The diagnosis of PD depends upon the presence of one or more of the four most common motor symptoms of the disease. In addition, there are other secondary and nonmotor symptoms that affect many people and are increasingly recognized by doctors as important to treating Parkinson’s.

Each person with Parkinson's will experience symptoms differently. For example, many people experience tremor as their primary symptom, while others may not have tremors, but may have problems with balance. Also, for some people the disease progresses quickly, and in others it does not.

By definition, Parkinson’s is a progressive disease. Although some people with Parkinson’s only have symptoms on one side of the body for many years, eventually the symptoms begin on the other side. Symptoms on the other side of the body often do not become as severe as symptoms on the initial side.

Find out more by reading detailed descriptions of Parkinson's symptoms below:

Primary Movement or “Motor” Symptoms

Resting Tremor: In the early stages of the disease, about 70 percent 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. A typical onset is tremor in one finger. The tremor consists of a shaking or oscillating movement, and usually appears when a person's muscles are relaxed, or at rest, hence the term "resting tremor." The affected body part trembles when it is not performing an action. Typically, the fingers or hand will tremble when folded in the lap, or when the arm is held loosely at the side, i.e., when the limb is at rest. The tremor usually ceases when a person begins an action. Some people with PD have noticed that they can stop a hand tremor by keeping the hand in motion or in a flexed grip. The tremor of PD can be exacerbated by stress or excitement, sometimes attracting unwanted notice. The tremor often spreads to the other side of the body as the disease progresses, but usually remains most apparent on the initially affected side. Although tremor is the most noticeable outward sign of the disease, not all people with PD will develop tremor.
Bradykinesia: Bradykinesia means “slow movement.” A defining feature of Parkinson’s, bradykinesia also describes a general reduction of spontaneous movement, which can give the appearance of abnormal stillness and a decrease in facial expressivity. Bradykinesia causes difficulty with repetitive movements, such as finger tapping. Due to bradykinesia, a person with Parkinson’s may have difficulty performing everyday functions,such as buttoning a shirt, cutting food or brushing his or her teeth. People who experience bradykinesia may walk with short, shuffling steps. The reduction in movement and the limited range of movement caused by bradykinesia can affect a person’s speech, which may become quieter and less distinct as Parkinson’s progresses.
Rigidity: Rigidity causes stiffness and inflexibility of the limbs, neck and trunk. Muscles normally stretch when they move, and then relax when they are at rest. In Parkinson’s rigidity, the muscle tone of an affected limb is always stiff and does not relax, sometimes contributing to a decreased range of motion. People with PD most commonly experience tightness of the neck, shoulder and leg. A person with rigidity and bradykinesia tends to not swing his or her arms when walking. Rigidity can be uncomfortable or even painful.
Postural Instability: One of the most important signs of Parkinson’s is postural instability, a tendency to be unstable when standing upright. A person with posturalinstability has lost some of the reflexes needed for maintaining an upright posture, and may topple backwards if jostled even slightly. Some develop a dangerous tendency to sway backwards when rising from a chair, standing or turning. This problem is called retropulsion and may result in a backwards fall. People with balance problems may have particular difficulty when pivoting or making turns or quick movements. Doctors test postural stability by using the “pull test.” During this test, the neurologist gives a moderately forceful backwards tug on the standing individual and observes how well the person recovers. The normal response is a quick backwards step to prevent a fall; but many people with Parkinson’s are unable to recover, and would tumble backwards if the neurologist were not right there to catch him or her.

Secondary Motor Symptoms

In addition to the cardinal signs of Parkinson’s, there are many other motor symptoms associated with the disease.

Freezing: Freezing of gait is an important sign of PD that is not explained by rigidity or bradykinesia. People who experience freezing will normally hesitate before stepping forward. They feel as if their feet are glued to the floor. Often, freezing is temporary, and a person can enter a normal stride once he or she gets past the first step. Freezing can occur in very specific situations, such as when starting to walk, when pivoting, when crossing a threshold or doorway, and when approaching a chair. For reasons unknown, freezing rarely happens on stairs. Various types of cues, such as an exaggerated first step, can help with freezing. Some individuals have severe freezing, in which they simply cannot take a step. Freezing is a potentially serious problem in Parkinson’s disease, as it may increase a person’s risk of falling forward.
Micrographia: This term is the name for a shrinkage in handwriting that progresses the more a person with Parkinson’s writes. This occurs as a result of bradykinesia, which causes difficulty with repetitive actions. Drooling and excess saliva result from reduced swallowing movements.
Mask-like Expression: This expression, found in Parkinson’s, meaning a person’s face may appear less expressive than usual, can occur because of decreased unconscious facial movements. The flexed posture of PD may result from a combination of rigidity and bradykinesia.
Unwanted Accelerations: It is worth noting that some people with Parkinson’s experience movements that are too quick, not too slow. These unwanted accelerations are especially troublesome in speech and movement. People with excessively fast speech, tachyphemia, produce a rapid stammering that is hard to understand. Those who experience festination, an uncontrollable acceleration in gait, may be at increased risk for falls.

Additional secondary motor symptoms include those below, but not all people with Parkinson’s will experience all of these.

Stooped posture, a tendency to lean forward
Dystonia
Impaired fine motor dexterity and motor coordination
Impaired gross motor coordination
Poverty of movement (decreased arm swing)
Akathisia
Speech problems, such as softness of voice or slurred speech caused by lack of muscle control
Difficulty swallowing
Sexual dysfunction
Cramping
Drooling

Nonmotor Symptoms

Most people with Parkinson’s experience nonmotor symptoms, those that do not involve movement, coordination, physical tasks or mobility. While a person’s family and friends may not be able to see them, these “invisible” symptoms can actually be more troublesome for some people than the motor impairments of PD.

Early Symptoms

Many researchers believe that nonmotor symptoms may precede motor symptoms — and a Parkinson’s diagnosis — by years. The most recognizable early symptoms include:

loss of sense of smell, constipation
REM behavior disorder (a sleep disorder)
mood disorders
orthostatic hypotension (low blood pressure when standing up).

If a person has one or more of these symptoms, it does not necessarily mean that individual will develop Parkinson’s, but these markers are helping scientists to better understand the disease process.

Other Nonmotor Symptoms

Some of these important and distressing symptoms include:

sleep disturbances
constipation
bladder problems
sexual problems
excessive saliva
weight loss or gain
vision and dental problems
fatigue and loss of energy.
depression
fear and anxiety
skin problems
cognitive issues, such as memory difficulties, slowed thinking, confusion and in some cases, dementia
medication sde effects, such as impulsive behaviors

Causes

What Causes Parkinson's?

To date, despite decades of intensive study, the causes of Parkinson’s remain unknown. Many experts think that the disease is caused by a combination of genetic and environmental factors, which may vary from person to person.

In some people, genetic factors may play a role; in others, illness, an environmental toxin or other event may contribute to PD. Scientists have identified aging as an important risk factor; there is a two to four percent riskfor Parkinson’s among people over age 60, compared with one to two percent in the general population.

The chemical or genetic trigger that starts the cell death process in dopamine neurons is the subject of intense scientific study. Many believe that by understanding the sequence of events that leads to the loss of dopamine cells, scientists will be able to develop treatments to stop or reverse the disease

Genetics and Parkinson's Disease: What Have We Learned?

By Katrina Gwinn, M.D.
Originally published in the Winter 2009 issue of PDF's Newsletter, News & Review.

You may have noticed a surge in stories about genetic testing and about specific genes that have been discovered to play a role in diseases. These discoveries, made mostly in the decade since the human genome was successfully sequenced, include 13 gene mutations that are associated with Parkinson’s disease (PD).

Whether it is you or your loved one who is living with Parkinson’s, you may be wondering how the new genetic discoveries will affect you and what they mean for your own risk or that of your children. In the long run, scientists hope that the knowledge provided by genetics will help us both to diagnose Parkinson’s earlier and to slow or stop its progression. They also hope that genetic studies will help us better predict who is at risk for Parkinson’s disease, so that interventions can take place before someone develops its symptoms — but we aren’t there yet.

Understanding Two Categories of Genes

To understand how genes are linked to Parkinson’s, begin by thinking of them in two categories. The first, “causal genes,” actually cause the disease. A causal gene alone, without the influence of other genes or environmental factors, guarantees that a person who inherits it will develop PD. This kind of genetic Parkinson’s is very rare, accounting for perhaps one to two percent of people with PD.

The second category of genes, “associated genes,” do not cause Parkinson’s on their own, but increase the risk of developing it. A person may have these genes and never develop PD, while people who do not have these genes can still end up being diagnosed with Parkinson’s. However, those who have the gene are more likely to develop PD then those without it. In order for associated genes to trigger PD, they probably need to be combined with other genes or environmental factors. For example, having genes for fair skin increases your risk of developing skin cancer, but whether you actually develop cancer will depend upon other factors, such as whether or not you spend a lot of time in the sun.

Scientists discovered both kinds of genes by studying families in which many members have developed Parkinson’s. It may be helpful to look at some of these families and how they have been affected by genetics.

Causal Genes: Alpha-synuclein

The ‘Iowa kindred’ or ‘Spellman-Muenter kindred,’ as it is known to PD researchers, is a large family in Iowa in which a specific gene for Parkinson’s was found. My colleagues and I traced 200 members of the family, including those who developed PD, back to the 1800s and we reviewed medical records dating back to about 1914. Then, taking DNA from blood samples provided by members of the current generation, we tested the entire genome to figure out which genes are associated with PD in this family.

We discovered that the culprit gene in the Iowa kindred was one known as alpha-synuclein, which is located on chromosome 4. Normally, the chromosome carries only a single copy of the alpha-synuclein gene, but members of this family with Parkinson’s carried three copies of the gene. This extra dose of alpha-synuclein caused certain family members to develop Parkinson’s at a young age.

Even within a family whose members have the same disease-causing gene, individuals may have very different experiences with the disease. In the Iowa kindred, the member of the family who was oldest upon diagnosis was a 51-year-old woman with a form of Parkinson’s called Lewy body dementia (LBD). Her cousin, however, was just 24 years old when typical Parkinson’s symptoms emerged.

Comparing these two people who share the same Parkinson’s genes, but who experience it differently, can give us clues about the disease. We can hypothesize that the woman who developed LBD at 51 had a genetic or environmental factor that protected her for 20 or 30 years. If we can understand how she was protected from PD, this knowledge could provide valuable insights into how to slow the progress of PD.

Associated Genes: LRRK2

While the gene for alpha-synuclein actually caused Parkinson’s in members of the Iowa kindred, another gene called LRRK2 — the gene for the protein Dardarin — is only associated with PD. Mutations in the LRRK2 gene that lead to PD are most common in people of North African, Basque, Portuguese and Ashkenazi Jewish descent, but occur in almost all ethnic groups.

For LRRK2, there is great variability in the mutations that occur in the gene, as well as in their effects. Some people with LRRK2 mutations develop PD in their 30s or 40s, while others develop the disease in their 80s, and others never develop PD at all. In some cases, people with LRRK2 gene mutations develop dementia, while others develop a form of Parkinson’s that shares features with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. Understanding this variability — why some people develop certain disease features and others are protected — gives scientists clues about how PD starts and progresses.

Using Genetics to Diagnose and Treat Parkinson’s Disease

By discovering genes linked to Parkinson’s, scientists can develop tests to find out who is at risk of developing Parkinson’s and can begin to diagnose it early, even before symptoms are obvious. Once we find a treatment that can slow down Parkinson’s, as opposed to simply easing its symptoms, it will become important to assess genetic risk, and to make a diagnosis as early as possible in order to begin treatment. Genetic research can also provide clues to identifying new therapeutic targets for Parkinson’s disease.

Already, the identification of genes associated with PD has allowed scientists to better understand the disease. For example, the first gene mutation identified to cause Parkinson’s was the gene for alpha-synuclein, now known as Park 1. After its discovery, scientists began looking for the alpha-synuclein protein in the brains of people who had died with PD. They learned that Lewy bodies, the protein clumps that accumulate in dying brain cells, are full of alpha-synuclein. This insight into the basic biological cause of PD has led to ideas for treatments.

The Iowa family studies mentioned above demonstrated that three copies of a normal gene can cause PD. Once this was discovered, the original mutations were re-evaluated, and it was found that both genetic causes increased the amount of synuclein in the cell. Scientists realized that it was the amount of synuclein, not just the type, which led to disease. That understanding, in turn, is leading to strategies which may lessen the amount of synuclein in the cells of people with Parkinson’s. It is it hoped that someday in the future, this method may help lessen, or hopefully even reverse PD.

Assessing Your Genetic Risk

Am I at risk? Should I get tested? If you or your parent or sibling is living with PD, you have probably asked these questions. You may wonder whether you have passed on risk factors to your children or whether you yourself have inherited any risk. I can relate to this because my own father has Parkinson’s. Statistically, my risk is between four and nine percent higher than it would be for a person with no family history of disease. What does that really mean for me? What does it mean for my niece and nephew? The truth is, we don’t yet know. Plus, because we lack treatments to slow the development and progression of Parkinson’s, genetic testing is not part of routine clinical practice, but is restricted as a research tool. However, ongoing research will refine our knowledge and perhaps provide better answers to these important questions.

Looking Forward

The next time you see genetics and Parkinson’s in the news, I hope that you will better understand why this field is so exciting. Discovering Parkinson’s genes — both those that cause disease on their own and those that contribute to risk — is helping doctors to better understand PD, to identify the risk of Parkinson’s earlier and to treat it more effectively.

Environmental Factors and Parkinson's: What Have We Learned?

By Caroline M. Tanner, M.D., Ph.D.
Originally published in the Spring 2011 issue of PDF's Newsletter, News & Review.

Scientists generally agree that most cases of Parkinson’s disease (PD) result from some combination of nature and nurture — the interaction between a person’s underlying genetic make-up and his or her life activities and environmental exposures. A simple way to describe this is that “genetics loads the gun and environment pulls the trigger.” In this formulation, “environment” has a very broad meaning — that is, it refers to any and all possible causes other than those that are genetic in origin.

The interactions between genes and environment can be quite complex. Some environmental exposures may lower the risk of PD, while others may increase it. Similarly, some people have inherited a genetic makeup that makes them more or less susceptible to the effects of toxicants, or poisonous agents, than others. The effect of a combined exposure can be greater — or lower — than a single exposure. All of this means that the particular combination of factors leading to PD is likely to be unique for each person. These combinations, in different ways, may trigger a common series of biological changes that will ultimately lead to the disease.

Scientists are beginning to tease apart the non-genetic factors that influence PD risk. In particular, epidemiologists are working to identify differences in the experiences of people who develop PD, compared to those who do not. But identifying these risk factors can be difficult. And when we do identify them, they serve only as clues. They do not provide a direct explanation for the cause of Parkinson’s, so scientists must supplement these population studies with laboratory experiments.

The following is a list of some of the risk factors for which we have found some evidence of an association with PD. For the most part, it is too soon to make recommendations for how to prevent Parkinson’s based on this research. However, these results may help us to understand the causes of PD, and provide direction for future research and therapy development.

Potential Risk Factors

Age.  About one percent of people over age 60 have Parkinson's disease, compared with just 0.001 percent of people 45 or younger.

Gender.  Parkinson’s is more common in men than in women. It is not known whether this is due to genetic factors, hormones or differences in behavior.

Head Injury.  Traumatic brain injury — injury that results in amnesia or loss of consciousness — has been associated with an increased risk of developing Parkinson’s years after the injury. Laboratory studies suggest that such injury may provoke inflammation in the brain, which could lead to the development of PD.

Area of Residence.  There are differences in the geographic distribution of PD. These could be due to differences in environmental factors, some of which are referenced below, and differences in genetic risk factors. Alternatively, they could be traced to differences in the methods that are used to count people with PD. While studies are too few to provide definitive patterns, some have been suggested. For example, Parkinson’s prevalence is higher in the Inuit population in Denmark than it is among other Danes, possibly reflecting a greater dietary intake among the Inuits of persistent organic pollutants such as polychlorinated biphenyls, or PCBs (see page 7). In the agricultural California central valley, living in a home near to fields where the pesticides paraquat and maneb were used was associated with PD in one report. Another study reported greater incidence of PD in urban areas with high levels of industrial emissions of the metal manganese, and possibly copper (see more on page 7).

Occupation.  Certain occupational categories or job titles have been associated with a higher incidence of PD, but results have been inconsistent. The relationship between welding (the process of fusing substances, usually metals) and PD has been a recent focus of controversy. In some reports for example, studies of people who are referred for medicolegal evaluation (an examination to determine the legal aspects of a workplace) welding has been suggested to cause Parkinson’s symptoms or earlier onset of PD.

However, in most other studies, including several in large national occupational and disease registries, welding has not been associated with PD risk.

A higher frequency of PD has been associated with many other occupations, but only a few occupations have been associated with PD in multiple studies, including agricultural and industrial workers. By contrast, lower rates of Parkinson’s are associated with shift work and jobs involving vigorous physical work. While we can hypothesize that the agricultural or industrial jobs may involve greater exposure to toxicant chemicals, further study in other populations is needed to understand if certain occupations are actually associated with a higher risk of PD. Some of the studies investigating specific toxicant exposures are described in the next sections.

Pesticide Exposure.  Of all the chemical exposures that have been linked to Parkinson’s, pesticides have been reported the most consistently. Recent research has shown higher rates of Parkinson’s among people who were exposed to pesticides over a long period of time as part of their work. Investigating other types of pesticide exposure, such as home use, is more challenging. However, hobby gardening and home pesticide use have each been associated with PD in one report. Although few studies have identified specific pesticides as leading to PD, those that have been so identified include the insecticides rotenone and permethrin (used in clothing and mosquito netting to kill mosquitos); organochlorines such as beta-hexachlorocyclohexane (beta-HCH — used in the United States from the 1950s to the 1970s); and the herbicides paraquat and 2,4- dichlorophenoxyacetic acid (2,4-D). It is important to note that most people who are exposed to these pesticides do not go on to develop Parkinson’s. The herbicide 2,4-D is one of the chemicals making up Agent Orange, used as a defoliant during the Vietnam war era. Although Agent Orange has not been proven to cause PD, the US Department of Veterans Affairs has ruled that veterans with PD who served in Vietnam between January 9, 1962 and May 7, 1975 are eligible to receive disability compensation from the Veterans Administration.

Exposure to Metals. Occupational exposures to various metals have been suggested to be related to the development of PD. But long-term exposure to metals is not easily measured, and the results of studies measuring PD risk and specific metals have been inconsistent. For example, high dose manganese exposure, a metal mentioned earlier, is known to cause a form of parkinsonism called manganism. Whether there is a relationship between manganese exposure and PD has been a point of interest, with focus on welders who may be exposed to it. A recent review concluded that manganese is an unlikely cause of Parkinsonism in the US population of welders. Direct measurement of lead levels in bone and blood serum suggests a link between PD and lead exposure, with greater risk associated with greater lifetime exposure.

Solvents and Polychlorinated Biphenyls (PCBs).  Trichloroethylene (TCE) is a solvent used in many industries and is the most common organic contaminant in groundwater. Occupational exposure to TCE was found to be associated with Parkinson’s among workers whose factory jobs resulted in long-term (eight to 33 years) exposure to the solvent. In a study of discordant twins (that is, twin pairs in which just one of the members had PD), the twin who had been occupationally exposed to TCE was more likely to develop Parkinson’s than the one who had not. This link has also been observed in experiments in the laboratory.

Polychlorinated biphenyls (PCBs), mentioned earlier, are persistent organic pollutants that were used in industrial processes until the late 1970s. PCBs have been found in relatively high concentrations in the brains of people who had PD. Occupational exposure to PCBs has been associated with greater risk of Parkinson’s in women, but not in men, and those women who were exposed have shown evidence of injury to their dopamine systems (the systems disrupted in PD).

Genetic Predisposition.  Often, a person’s genetic makeup will help to determine the effect of an environmental exposure. For example, agricultural workers exposed to pesticides were at an increased risk of PD only if they also had inherited a reduced ability to metabolize toxicants. In another study, head injury was associated with a higher risk of Parkinson’s only in people with one form of a particular gene; in people without this particular gene variant, head injury was not associated with a higher risk of PD. Increasingly, epidemiologists and geneticists are working together to identify combinations of genes and environmental exposures that are related to PD.

Potential Protective Factors

Scientists have also found certain factors that may actually reduce the risk of developing Parkinson’s. As with risk factors, not enough is known about these and they should not be tried without the counsel of a doctor.

Coffee and tea. Drinking coffee or tea has been associated with a lower risk of Parkinson’s, most markedly so in men. Caffeine has direct effects on the brain, and some of these effects may help to cause a lower risk of PD.

Uric acid or urate. This chemical occurs naturally in blood. High levels, associated with diets high in certain foods, such as meats, can cause gout and kidney stones. However, researchers have found that men with uric acid levels in the high end of the normal range have a lower incidence of Parkinson’s. Men with PD who have uric acid in the high normal range have a slower rate of PD progression. In women, who typically have lower urate levels, the same effects are not established. A drug that increases blood urate is being studied in a clinical trial in PD.

Anti-inflammatory drugs.  Several studies have shown that people who regularly take anti-inflammatory drugs such as ibuprofen have a lower risk of Parkinson’s. Inflammation is thought to play a role in causing Parkinson’s, and reducing inflammation may explain the reduced PD risk.

Smoking.  Many studies have associated cigarette smoking with a decreased risk of PD. Researchers hypothesize that nicotine may block the damaging processes causing PD, but the exact effects are not known. A clinical trial to study nicotine in PD is planned.

Cholesterol levels.  Some studies have suggested that the use of statins — drugs that are used to lower cholesterol levels — is associated with reduced PD risk. However, in other studies an association was also found between low blood cholesterol levels and increased PD risk. Understanding cholesterol metabolism may provide clues to the molecular mechanisms that cause PD.

Body mass.  People with higher vitamin D levels were at lower risk of PD in one study. Vitamin D has many beneficial effects that, theoretically, could help to prevent PD, and Vitamin D receptors (recognition sites) are found in the brain areas damaged in PD.

Exercise. Greater physical activity has been associated with lower risk of Parkinson’s. Studies in animals also support this.

The Search for Proof

Observational studies cannot prove that an association is truly a cause of PD. This is because the kinds of studies that could pin down exact answers cannot be carried out on people. Instead, we must conduct experiments in the laboratory and then project the results of these tests as best we can to what happens in people. However, laboratory experiments can never give us the full picture of PD risk in humans. The final test can only be done through an iterative process, taking the clues gained from observations of human populations into the laboratory, and then bringing the laboratory results back again to the human population. Plausibility in the human framework provides the ultimate test for results from laboratory research. Our hope is that understanding environmental risk factors will lead to a better understanding not only of the causes of PD, but of other neurodegenerative disorders as well.

Medications & Treatments

There are many medications available to treat the symptoms of Parkinson’s, although none yet that actually reverse the effects of the disease.

It is common for people with PD to take a variety of these medications – all at different doses and at different times of day - in order to manage the symptoms of the disease.

While keeping track of medications can be a challenging task, understanding your medications and sticking to a schedule will provide the greatest benefit from the drugs and avoid unpleasant “off” periods due to missed doses.

Read more to understand each type of medication, its dosing and side effects. Interested in learning more about medications in the pipeline?

Coping with Symptoms

If you have gone to the doctor because of movement symptoms, you may not be aware — and your doctor may not tell you at the time you are diagnosed —that Parkinson’s disease manifests in many additional ways other than the more visible movement symptoms. Fatigue, constipation, and sleep problems are a few such examples of common non-movement symptoms of PD.

These symptoms, which are not related to movement, are called nonmotor symptoms of PD. They can also include mild cognitive impairment (such as difficulty focusing on a task), depression, soft speech, pain, and impulsive behaviors.

These symptoms are frequently more troubling, and interfere more with daily life, than motor signs. Effective therapies are available to treat these symptoms—medications as well as physical therapy, occupational therapy, and speech therapy.

Recognizing nonmotor symptoms, and understanding how they may affect your quality of life, is a first step toward taking control of your health and living well with Parkinson’s.

My Info Blog

Monday, September 5, 2011

Every Thing About Parkinson’s Disease