Parkinson’s Disease – Causes, Signs and symptoms

Parkinson Disease

Summary

Parkinson’s disease is a chronic, progressive disease that causes several characteristic symptoms, including tremors, slowness of movement and rigidity. As symptoms progress, patients with Parkinson’s may have difficulty performing basic tasks, including talking and walking.

Parkinson’s disease is the result of the gradual destruction of cells in the brain responsible for producing and releasing a neurotransmitter called dopamine. Dopamine controls movement and balance in the body and a sharp decline in the production of dopamine triggers the symptoms of Parkinson’s. It is not completely understood what causes the destruction of dopamine-producing cells in patients with Parkinson’s. However, experts suspect that an interaction between genes and environmental factors may play a role in the development of the disease.

Parkinson’s disease is both chronic and progressive, which means that it is a long-term condition that worsens over time. It typically begins in a person’s 50s or 60s and, for unknown reasons, occurs twice as often in men than women, according to the National Institutes of Health. Symptoms of Parkinson’s disease tend to emerge slowly and are often subtle at first. They usually affect just one side of the body initially, before moving to the other side of the body.

There are four major symptoms commonly associated with Parkinson’s disease. They are:

  • Tremor. A trembling in the hands, arms, legs, jaw and face.
  • Rigidity. Stiffness of the limbs and trunk.
  • Bradykinesia. Slowness of movement.
  • Postural instability. Impaired balance and coordination.

To date, no blood tests or other laboratory tests have been shown to accurately diagnose Parkinson’s disease. While diagnosis may be difficult, a neurological examination and other tests may provide clues to the presence of the illness.

Without treatment, patients usually experience a steady worsening of symptoms and a corresponding decline in quality of life. However, both the nature and severity of symptoms vary significantly from patient to patient, and overall prognosis is difficult to predict.

There is no cure for Parkinson’s disease. Medications are usually recommended and can substantially reduce a patient’s symptoms. While medications are often effective in reducing symptoms, they do not slow or stop the progression of the disease. If medications fail to alleviate symptoms, patients with advanced Parkinson’s disease may be advised to undergo brain surgery.

Typically, Parkinson’s disease cannot be prevented through lifestyle changes, although studies have also shown that caffeine consumption may be associated with a reduced risk of Parkinson’s disease in some people.

There are several areas of research that are currently being conducted on Parkinson’s disease. They include studies to identify the cause of the disease, as well as any potential treatment or prevention methods.

About Parkinson’s disease

Parkinson’s disease is chronic, progressive disease, which means it is a long-term condition in which the symptoms worsen over time. It causes several characteristic symptoms, including tremors, slowness of movement (bradykinesia) and limb and trunk rigidity. It is a motor system disorder. As symptoms progress, patients with Parkinson’s disease may have difficulty performing basic tasks, including talking and walking.

The condition was identified in 1817 by James Parkinson, a British physician who first described the principal symptoms of the disease.

Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease, according to the National Parkinson Foundation (NPF). Some estimates suggest that roughly 1 million people in the United States have Parkinson’s disease. However, the disease is often not diagnosed or misdiagnosed, so this figure may not be accurate. The NPF estimates that Parkinson’s disease affects one in every 100 people over the age of 60, and the average age of onset is 60. The National Institute of Neurological Disorders and Stroke (NINDS) estimates that “early-onset” (in which symptoms develop before the age of 50) Parkinson’s disease occurs in about 5 to 10 percent of people with Parkinson’s disease. These cases are often inherited, and scientists have linked several cases to identified gene mutations. In rare cases, symptoms may appear in people under 20, a condition known as juvenile parkinsonism.

For unknown reasons, more men than women are affected. The NINDS estimates that 50 percent more men than women have Parkinson’s disease.

In healthy people, cells within a small region of the brain stem known as the substantia nigra produce and release a neurotransmitter called dopamine, which controls movement and balance in the body. Dopamine is vital to proper central nervous system functioning and helps electrochemical signals move from one neuron to another.

However, patients with Parkinson’s disease experience a destruction of the cells in the substantia nigra. By the time 60 to 80 percent of these cells are destroyed, there is a sharp decline in dopamine production triggering the symptoms of Parkinson’s disease.

Recent studies also have found that destruction of the nerve endings that produce the neurotransmitter norepinephrine may contribute to many of the nonmotor-related symptoms of Parkinson’s disease. These include fatigue and blood pressure problems. Norepinephrine is the chief chemical messenger within the sympathetic nervous system (the part of the autonomic nervous system that controls automatic functions in the body).  

Some patients who appear to have Parkinson’s disease may actually have a separate disorder that mimics Parkinson’s disease. These disorders may be grouped with Parkinson’s disease and are collectively known as parkinsonism. Examples of non-Parkinson’s disease parkinsonism include:

  • Drug-induced parkinsonism. Caused by taking certain medications, including antipsychotics, calcium-channel blockers, the dopamine blocker metoclopramide and the blood pressure medication reserpine.
  • Vascular parkinsonism. Results from blockage of small blood vessels to the brain.
  • Essential tremor. A progressive condition that tends to run in families and usually affects both hands, particularly when the hands are moving. It may affect the head as well. Patients with this condition usually do not have other parkinsonian features.
  • Lewy body dementia. Condition marked by early dementia, hallucinations and fluctuations in cognitive status.
  • Multiple system atrophy. An illness that causes symptoms similar to Parkinson’s disease, but it is much less common and tends to develop more rapidly. The cause of this neurodegenerative disease is unknown.
  • Other conditions. Parkinsonian symptoms may appear in patients with other neurological disorders, including Wilson’s disease, Huntington’s disease, Alzheimer’s disease, spinocerebellar ataxias and Creutzfeldt-Jakob disease.  

Without treatment, patients with Parkinson’s disease usually experience a steady worsening of symptoms and a corresponding decline in quality of life. However, both the nature and severity of symptoms vary significantly from patient to patient, and overall prognosis usually is difficult to predict. Generally, most people with Parkinson’s disease have a similar life expectancy to healthy people. However, some of the symptoms of Parkinson’s disease (e.g., difficulties chewing and swallowing) may cause choking and aspiration pneumonia, which can be fatal.

Risk factors and causes of Parkinson’s disease

It is not completely understood what causes Parkinson’s disease. However, experts suspect that the development of Parkinson’s disease is a result of interaction between genes and the environment. Toxins that have yet to be identified are believed to build up in a person’s body over time and may trigger Parkinson’s disease in people who are genetically predisposed to the illness.

Possible environmental factors that have been associated with Parkinson’s disease include rural living, exposure to well water and participation in agricultural work. This has led some experts to conclude that pesticides and herbicides may contribute to Parkinson’s disease. However, it is important to stress that many people with Parkinson’s disease have not been exposed to any of these risk factors.

Viruses may be another potential source of Parkinson’s disease. In 1918, some people who developed encephalitis (brain disease) as a result of the influenza epidemic later went on to develop symptoms resembling Parkinson’s disease. Women in Taiwan are believed to have developed similar symptoms as a result of exposure to the herpes virus. Scientists have not established the precise link between viruses and the development of Parkinson’s disease.

Some research also suggests a link between Parkinson’s disease and damage caused by free radicals. Free radicals are molecules that damage parts of the cells. This damage is known as oxidative stress and is believed to play a part in the development of numerous diseases including Alzheimer’s disease and some forms of cancer.

Several genes have been linked to Parkinson’s disease, including a gene called parkin that helps break down defective proteins inside neurons. An altered parkin gene may prevent the breakdown of these proteins. As these proteins accumulate, they are believed to contribute to the destruction of neurons. However, genetic mutations are believed to account for only a small percentage of all cases of Parkinson’s disease.

The risk of developing Parkinson’s disease increases as a person ages. The average age of onset is 60, according to the National Parkinson Foundation (NPF). Roughly 5 to 10 percent of patients develop the illness at age 50 or younger, according to the National Institute of Neurological Disorders and Stroke (NINDS). Gender also appears to be a risk factor. According to the NINDS, Parkinson’s disease occurs twice as often among men than women, although the reasons for this are unclear.

People with a family history of Parkinson’s disease – particularly a first-degree relative who has had the disease – have significantly higher risk of developing Parkinson’s disease. It is believed that between 15 and 25 percent of patients with Parkinson’s disease have a family history of the disease, according to the NINDS.

Signs and symptoms of Parkinson’s disease

Symptoms of Parkinson’s disease tend to emerge slowly and are often subtle at first. However, in some patients, they may progress quickly. Symptoms usually affect just one side of the body initially before moving to the other side. Even when the symptoms begin to affect both sides of the body, the patient usually experiences more severe symptoms on one side than the other.  

There are four major symptoms commonly associated with Parkinson’s disease. They are:

  • Tremor. A trembling in the hands, arms, legs, jaw and face. The tremors are most obvious when a person is at rest. In Parkinson’s disease, the tremor often appears as a characteristic back-and-forth motion that occurs at the rate of between four and six beats per second. It also often involves rubbing of the thumb and forefinger that is described as a “pill rolling” motion.
  • Rigidity. A stiffness of the limbs and trunk that results from muscles being constantly tensed and contracted. It is most obvious when another person tries to move the patient’s arm, which typically responds in short and jerky movements. This is known as cogwheel rigidity.
  • Bradykinesia. Slowness of movement. People with Parkinson’s disease may take several hours to perform simple tasks such as washing or dressing.
  • Postural instability. Impaired balance and coordination. Patients often fall easily and may develop a stooped posture.

Patients who display these symptoms are said to have parkinsonism. This term encompasses both Parkinson’s disease and other disorders that mimic Parkinson’s disease but that are caused by other factors (e.g., taking certain medications or having Lewy body dementia). When symptoms first appear, it is usually unclear whether patients have Parkinson’s disease or one of these other conditions.

Some people with Parkinson’s disease display all the symptoms of the disease, although certain symptoms may be more pronounced. Tremors are the most characteristic symptom of Parkinson’s disease. However, some people with Parkinson’s disease experience very mild or nonexistent tremors.

Because Parkinson’s disease usually develops gradually, patients may be unaware of their symptoms at first. They may notice that they have a slight tremor in one hand or that their handwriting seems smaller and more cramped than usual. Friends and family members may also notice that the patient moves unusually slowly or has a blank facial expression.

As symptoms progress, patients with Parkinson’s disease may find that their tremor interferes with daily activities. They may also have difficulty chewing, swallowing and speaking. Urinary problems, constipation and skin conditions (e.g., oily or dry skin, excessive sweating) are also associated with this disease.

Other motor symptoms associated with Parkinson’s disease include:

  • Difficulty initiating any voluntary movement
  • Difficulty arising after sitting
  • Difficulty turning in bed
  • Shuffling walk
  • Small steps followed by a brief run to maintain balance while walking
  • Reduced swinging of the arms
  • Lack of facial expression or animation in the face
  • Small handwriting (micrographia)

Other nonmotor-related symptoms associated with Parkinson’s disease include:

  • Drooling
  • Erectile dysfunction in men
  • Foot cramps
  • Increased perspiration
  • Lower voice volume
  • Reduced sense of smell

Some patients with Parkinson’s disease develop dementia as the disease progresses. This condition, called Parkinson’s dementia, may cause memory loss, difficulties with language and lack of social judgment. 

Patients who are diagnosed with Parkinson’s disease often experience great anxiety about the progressive nature of the disease and may excessively monitor their symptoms. Others may begin to avoid social situations for fear of being embarrassed by their condition. Some patients may experience sleep disturbances, depression (which may be exacerbated by the loss of dopamine that occurs with Parkinson’s disease) and other emotional changes as the disease progresses.

Diagnosis methods for Parkinson’s disease

In diagnosing Parkinson’s disease, a physician will compile a thorough medical history and perform a complete physical examination. To date, no blood tests or other laboratory tests have been shown to accurately diagnose Parkinson’s disease.

While diagnosis may be difficult, a neurological examination may provide clues to the presence of the illness. The physician will also look for at least two of the following three signs: tremor when the patient is at rest, slowness of movement (bradykinesia) or rigidity. Various tests can be used to reveal the presence of these symptoms. For example, patients may be asked to tap a finger and thumb together or tap their foot to look for signs of bradykinesia. Meanwhile, postural instability is tested by asking patients to retain their balance while they are pulled backwards by the physician.

Physicians may recommend a brain scan, using imaging technology such as magnetic resonance imaging (MRI), to rule out other conditions that can cause similar symptoms.

Parkinson’s disease is diagnosed when a combination of a patient’s medical history, symptoms and test results indicate illness that cannot be explained by other factors or diseases.

Treatment options for Parkinson’s disease

There is no cure for Parkinson’s disease. Medications are usually recommended and can substantially reduce a patient’s symptoms. Most medications are aimed at increasing the levels or reducing the breakdown of dopamine in the brain. However, it is not possible to take dopamine in pill form because the chemical is broken down before it can reach the brain.  

Most patients receive a combination of the drugs levodopa and carbidopa to treat the symptoms of Parkinson’s disease. Neurons inside the body convert levodopa to dopamine, and carbidopa helps to ensure that this process does not happen until the levodopa reaches the brain. Carbidopa also helps reduce side effects that are associated with levodopa, such as nausea and vomiting. Other side effects of levodopa include dyskinesia (uncontrollable movements), sudden sleep onset, hallucinations and psychosis.  

Most patients who take this medication gain some benefit from it, according to the National Institute of Neurological Disorders and Stroke (NINDS). Usually, these drugs have the most significant impact on rigidity and slowness of movement. They are also effective in reducing tremors. However, they may have little or no effect on other symptoms, such as postural instability or nonmotor-related symptoms. They also do not repair or replace damaged nerve cells in the brain, nor do they stop progression of the disease. 

The benefits of levodopa therapy are usually experienced soon after beginning the medication, although the dosage may be gradually increased over time in order to be most effective. Levodopa can dramatically increase the quality of life for people with Parkinson’s disease. However, it is not a cure for Parkinson’s disease and cannot slow the progression of the disease. Eventually, the effectiveness of levodopa therapy may decrease, in which case patients usually experience a gradual worsening of symptoms (called the “wearing off effect”) or periodic attacks of more severe symptoms (called the “on-off effect”).  

Other drugs may be used to treat the symptoms of Parkinson’s disease or increase the effectiveness of levodopa. These may include:

  • Dopamine agonists. These drugs treat Parkinson’s disease by mimicking the effects of dopamine on target cells. They are sometimes used in conjunction with levodopa. Although they are generally considered safe, the side effects from this type of medication can include sleep disorders, hallucinations, confusion and nightmares. They have also been linked to compulsive behavior (e.g., gambling, hypersexuality, excessive shopping) in some patients.

  • COMT inhibitors and MAO-B inhibitors. These drugs inhibit the breakdown of dopamine caused by the enzymes catechol-O-methyltransferase (COMT) and monoamine oxidase B (MAO-B). They are often used to extend the effectiveness of levodopa. The most common side effect from these medications is diarrhea. People who are taking certain other drugs (e.g., the antidepressant fluoxetine or the pain medication mepiridine) should consult their physician before taking certain MAO-B inhibitors as they may have harmful interactions.

  • Anticholinergics. These drugs are primarily used to treat tremors and muscle rigidity. They work by reducing the effects of the neurotransmitter acetylcholine. It is thought that excess levels of acetylcholine increase neuron activity in the brain and that, by reducing these levels, anticholinergics may be effective in controlling tremors and muscle rigidity. However, anticholinergics are only effective in roughly half of the patients who use them, according to the NINDS. Even for people who respond well to anticholinergics, the medication usually offers limited benefits for a short period of time. Side effects may include dry mouth, constipation, urinary retention, hallucinations and delirium.

  • Amantadine. This drug may be used to treat the symptoms of Parkinson’s disease, as well as some of the side effects of levodopa, such as dyskinesia. Amantadine is an antiviral drug that is sometimes used to treat certain types of influenza. It is not fully understood how the drug works to control symptoms of Parkinson’s disease, although it is thought to increase the effects of dopamine. Side effects may include insomnia, mottled skin and hallucinations.

If medications fail to alleviate symptoms, patients with advanced Parkinson’s disease may be advised to undergo surgery. One of the most common procedures is a form of surgery called deep brain stimulation. In this procedure, electrodes are placed in the brain and connected to a small electrical device (called a pulse generator) that is surgically implanted in the chest wall. The pulse generator delivers electrical stimulation to specific parts of the brain in order to reduce the patient’s symptoms. The device can be controlled by the patient and reprogrammed by a physician as needed. 

It is important to note that not all patients are good candidates for surgery. Deep brain stimulation has been shown to be more effective on younger patients with Parkinson’s disease and is generally not suitable for patients who are in poor overall health. However, some older patients in good health have benefited from deep brain stimulation.

Another form of surgery, known as a pallidotomy or thalamotomy (depending on the area of the brain targeted), involves the destruction of parts of the brain that are associated with the symptoms of Parkinson’s disease. During this procedure, surgeons use radio frequency energy to heat and destroy the globus pallidus (pallidotomy) or the thalamus (thalamotomy). Abnormal activity in these two small areas in the brain is believed to contribute to movement problems in people with Parkinson’s disease.

Because of the risks with radiofrequency destruction of the globus pallidus or thalamus, deep brain stimulation is usually a preferred treatment method over pallidotomy and thalamotomy for patients with advanced Parkinson’s disease.

Surgery may improve many of the symptoms of Parkinson’s disease. However, patients may find that they still have to rely on medication to effectively control symptoms. They may also still have to take medication to treat symptoms that are not affected by surgery, such as nonmotor-related symptoms. 

Physical therapy and occupational therapy can help patients learn new ways to cope with their symptoms. Physical therapy includes a mixture of exercise, massage and other treatments to maintain strength and flexibility. A physical therapist is likely to teach the patient exercises that can be performed at home to strengthen and retrain muscles. This helps patients improve balance and reduce fatigue. Occupational therapy is similar to physical therapy, but it focuses on improving patients’ fine motor skills so they can better accomplish daily activities, such as dressing and bathing.

Patients are encouraged to engage in complementary or supportive therapies, such as eating a well-balanced diet and exercising regularly. Eating a diet that is high in fiber and consuming plenty of fluids can help reduce constipation, which can be associated with Parkinson’s disease. Additionally, patients who remain active may better cope with the disabling nature of the disease.

Finally, some patients and their caregivers may find that support groups or individual counseling are helpful when coping with Parkinson’s disease. This type of therapy may be a valuable outlet for both the patient and the patient’s caregiver to discuss feelings of frustration or depression.

Prevention methods for Parkinson’s disease

ypically, Parkinson’s disease cannot be prevented through behavioral changes. However, numerous studies have shown that people who smoke are less likely to develop Parkinson’s disease. While smoking may confer a small amount of protection against Parkinson’s disease, the health risks associated with tobacco use far outweigh any minor benefits and is not encouraged.

Studies have also shown that caffeine consumption may be associated with reduced risk of Parkinson’s disease in some people. However, women undergoing hormone replacement therapy may have an increased risk of Parkinson’s disease if they consume more than five cups of a caffeinated beverage per day.

Ongoing research about Parkinson’s disease

Much of the research surrounding Parkinson’s disease is focused on preventing or slowing the progression of the disease. Scientists are attempting to find evidence of biochemical abnormalities (biomarkers) that are common in patients with Parkinson’s disease. In the future, tests may be developed to screen people for these biomarkers and predict the occurrence of Parkinson’s disease. The identification of biomarkers may also be useful for developing new treatment or prevention methods.

Research is also being conducted on the importance of genes in the development of Parkinson’s disease. Scientists have identified several genes that are related to Parkinson’s disease. However, there are believed to be many more. It is hoped that by understanding more about the role that genes play in the development of Parkinson’s disease, scientists may be able to better prevent the disease.

Scientists are also continuing to explore new techniques of treating Parkinson’s disease. For example, fetal substantia nigra cells (which produce and release dopamine) have been transplanted into hundreds of patients with Parkinson’s disease. To date, results have been mixed. Younger patients tend to fare better than older patients, and side effects have been significant for some patients, including the development of intractable dyskinesia (uncontrolled movements). Additionally, cells from tissue at the back of the eye (called retinal pigment epithelial cells), which also produce dopamine, have also been used in transplants. This procedure shows promise.

Stem cell therapy has also been studied in relation to Parkinson’s disease. Stem cells differ from others in the body because they create cells with specific purposes. For example, some stem cells are cardiac stem cells and will only make heart muscle cells. Other stem cells create brain tissue cells or lung tissue cells. Some types of stem cells, called embryonic stem cells, may be used to create any type of cell. Scientists are researching whether embryonic stem cells may be used to create dopamine-producing cells.

Treatment techniques considered to be highly experimental include gene therapy (the transplantation of genetically altered genes to replace defective genes) and delivery of growth factor (a substance that encourages the growth of cells) to certain areas of the brain.

Several new drug treatments that aim to increase dopamine levels in the brain are undergoing clinical trials for use by patients with Parkinson’s disease. Testing is also under way to discover whether certain drugs have neuroprotective qualities and may be able to slow the progression of Parkinson’s disease. Additionally, scientists are researching whether supplements such as vitamin B12 might be helpful for patients with Parkinson’s disease.

Questions for your doctor

Preparing questions in advance can help patients to have more meaningful discussions with healthcare professionals regarding their condition. Patients may wish to ask their doctor the following questions related to Parkinson’s disease:

  1. What are the first symptoms of Parkinson’s disease that I am likely to notice?
  2. How do you know that I have Parkinson’s disease and not another disease?
  3. How fast is my disease likely to progress?
  4. Which medications do you recommend I take to treat my Parkinson’s disease?
  5. How long will it take for these medications to work?
  6. Which symptoms of mine will the medications treat?
  7. How long is my medication likely to be effective?
  8. Is surgery an option for me?
  9. What signs should I look for that might indicate my condition is worsening?
  10. What is my long-term prognosis?
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