Parkinson's disease (PD) is a degenerative disorder of the central nervous system mainly affecting the motor system. Early in the course of the disease, the most obvious symptoms are movement-related; these include shaking, rigidity, slowness of movement and difficulty with walking and gait. Later, thinking and behavioral problems may arise, with dementia commonly occurring in the advanced stages of the disease, and depression being the most common psychiatric symptom. Other symptoms include sensory, sleep, and emotional problems. The main motor symptoms are collectively called "parkinsonism", or a "parkinsonian syndrome".
The disease can be either primary or secondary. Primary Parkinson's disease has no known cause, although some atypical cases have a genetic origin. Secondary parkinsonism is due to known causes like toxins. Many risks and protective factors have been investigated: the clearest evidence is for an increased risk in people exposed to certain pesticides and a reduced risk in tobacco smokers. The motor symptoms of the disease result from the death of cells in the substantia nigra, a region of the midbrain. This results in not enough dopamine in these areas. The reason for this cell death are poorly understood but involves the build-up of proteins into Lewy bodies in the neurons. Where the Lewy bodies are located is partly related to the expression and degree of the symptoms. Diagnosis of typical cases is mainly based on symptoms, with tests such as neuroimaging being used for confirmation.
Treatments, typically the antiparkinson medications L-DOPA and dopamine agonists, improve the early symptoms of the disease. As the disease progresses and neurons continue to be lost, these medications become ineffective while at the same time produce a complication marked by involuntary writhing movements. Diet and some forms of rehabilitation have shown some effectiveness at improving symptoms. Surgery to place deep brain stimulation has been used to reduce motor symptoms in severe cases where drugs are ineffective. Research directions include investigations into new animal models of the disease and of the potential usefulness of gene therapy, stem cell transplants, and neuro-protective agents . Medications to treat non-movement-related symptoms of PD, such as sleep disturbances and emotional problems, also exist.
In 2013 PD was present in 53 million people and resulted in about 103,000 deaths globally. Parkinson's disease is more common in older people, with most cases occurring after the age of 50; when it is seen in young adults, it is called young onset PD. The disease is named after the English doctor James Parkinson, who published the first detailed description in An Essay on the Shaking Palsy, in 1817. Several major organizations promote research and improvement of quality of life of those with the disease and their families. Public awareness campaigns include Parkinson's disease day (on the birthday of James Parkinson, 11 April) and the use of a red tulip as the symbol of the disease. People with parkinsonism who have increased the public's awareness of the condition include actor Michael J. Fox, Olympic cyclist Davis Phinney, and late professional boxer Muhammad Ali.
The specific group of symptoms that an individual experiences varies from person to person. Primary motor signs of Parkinson’s disease include the following.
tremor of the hands, arms, legs, jaw and face
bradykinesia or slowness of movement
rigidity or stiffness of the limbs and trunk
postural instability or impaired balance and coordination
Scientists are also exploring the idea that loss of cells in other areas of the brain and body contribute to Parkinson’s. For example, researchers have discovered that the hallmark sign of Parkinson’s disease — clumps of a protein alpha-synuclein, which are also called Lewy Bodies — are found not only in the mid-brain but also in the brain stem and the olfactory bulb.
These areas of the brain correlate to non-motor functions such as sense of smell and sleep regulation. The presence of Lewy bodies in these areas could explain the non-motor symptoms experienced by some people with PD before any motor sign of the disease appears. The intestines also have dopamine cells that degenerate in Parkinson’s, and this may be important in the gastrointestinal symptoms that are part of the disease.
How is Parkinson’s Diagnosed?
Making an accurate diagnosis of Parkinson’s — particularly in its early stages — is difficult, but a skilled practitioner can come to a reasoned conclusion that it is PD. You may have experienced this frustration. Perhaps it took years for you to receive a diagnosis. Perhaps you have been diagnosed, but with Parkinsonism, not Parkinson's, and are confused about the implications.
To diagnose Parkinson’s, the physician takes a careful neurological history and performs an examination. There are no standard diagnostic tests for Parkinson’s, so the diagnosis rests on the clinical information provided by the person with Parkinson’s and the findings of the neurological exam.
The doctor looks to see if your expression is animated.
Your arms are observed for tremor, which is present either when they are at rest, or extended.
Is there stiffness in your limbs or neck?
Can you rise from a chair easily?
Do you walk normally or with short steps, and do your arms swing symmetrically? The doctor will pull you backwards.
How quickly are you able to regain your balance?
The main role of any additional testing is to exclude other diseases that imitate Parkinson’s disease, such as stroke or hydrocephalus. Very mild cases of PD can be difficult to confirm, even by an experienced neurologist. This is in part because there are many neurological conditions that mimic the appearance of Parkinson’s.
A person’s good response to levodopa (which temporarily restores dopamine action in the brain) may support the diagnosis. But this is not relevant if your doctor thinks you do not need any medication at this time. If you are in doubt of your diagnosis or if you need further information, you may want to seek a second opinion.
Tests to Diagnose Parkinson’s
There is no standard diagnostic test for Parkinson’s. Researchers are working to develop an accurate “biological marker,” such as a blood test or an imaging scan. To date, the best objective testing for PD consists of specialized brain scanning techniques that can measure the dopamine system and brain metabolism. But these tests are performed only in specialized imaging centers and can be very expensive.
DaTscan for Parkinson's
Young Onset Parkinson's
Parkinsonisms and Parkinson's Plus Syndromes
What Causes Parkinson's?
Parkinson's disease in most people is idiopathic (having no specific known cause). However, a small proportion of cases can be attributed to known genetic factors. Other factors have been associated with the risk of developing PD, but no causal relationships have been proven.
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 risk for 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
The progression of Parkinson’s disease varies among different individuals. Parkinson's is chronic and slowly progressive, meaning that symptoms continue and worsen over a period of years. Parkinson's is not considered a fatal disease. And the way that it progresses is different for everyone:
Movement symptoms vary from person to person, and so does the pace at which they progress.
Some are more bothersome than others depending on what a person normally does during the day.
Some people with Parkinson's live with mild symptoms for many years, whereas others develop movement difficulties more quickly.
Nonmotor symptoms also are very individualized, and they affect most people with Parkinson's at all stages of disease. Some people with Parkinson's find that symptoms such as depression or fatigue interfere more with daily life than do problems with movement.
That said, there are tools that your doctor may use to understand the progression of your Parkinson's. The stages of Parkinson's correspond both to the severity of movement symptoms and to how much the disease affects a person’s daily activities. The most commonly used rating scales are focused on the motor symptoms, but new scales include information on non-motor symptoms (such as problems with sense of smell).
The first, known as Hoehn and Yahr, will rate your symptoms on a scale of 1 to 5. On this scale, depending on a person’s difficulties, 1 and 2 represent early-stage, 2 and 3 mid-stage, and 4 and 5 advanced-stage Parkinson's.
Another scale commonly used to assess the progression of Parkinson's is the United Parkinson’s Disease Rating Scale (UPDRS). It is more comprehensive than the Hoehn and Yahr scale, which focuses on movement symptoms. In addition to these, the UPDRS takes into account cognitive difficulties, ability to carry out daily activities, and treatment complications.
Severity of Parkinson's
Below are some descriptions of mild, moderate and advanced Parkinson's. As disease progresses differently in different people, many do not progress to the advanced stage.
Movement symptoms may be inconvenient, but do not affect daily activities
Movement symptoms, often tremor, occur on one side of the body
Friends may notice changes in a person’s posture, walking ability or facial expression
Parkinson's medications suppress movement symptoms effectively
Regular exercise improves and maintains mobility, flexibility, range of motion and balance, and also reduces depression and constipation
Movement symptoms occur on both sides of the body
The body moves more slowly
Trouble with balance and coordination may develop
“Freezing” episodes — when the feet feel stuck to the ground — may occur
Parkinson's medications may “wear off” between doses
Parkinson's medications may cause side effects, including dyskinesias (involuntary movements)
Regular exercise, perhaps with physical therapy, continues to be important for good mobility and balance
Occupational therapy may provide strategies for maintaining independence
Great difficulty walking; in wheelchair or bed most of the day
Not able to live alone
Assistance needed with all daily activities
Cognitive problems may be prominent, including hallucinations and delusions
Balancing the benefits of medications with their side effects becomes more challenging
At all stages of Parkinson's, effective therapies are available to ease symptoms and make it possible for people with Parkinson's to live 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.
Currently, there are two surgical treatments available for people living with Parkinson’s disease — deep brain stimulation (DBS) and surgery performed to insert a tube in the small intestine, which delivers a gel formulation of carbidopa/levodopa (Duopa™).
Deep Brain Stimulation
DBS surgery was first approved in 1997 to treat Parkinson’s disease tremor, then in 2002 for the treatment of advanced Parkinson's disease symptoms. More recently, in 2016, DBS surgery was approved for the earlier stages of Parkinson's, for those with at least four years disease duration and with motor complications that are not adequately controlled with medication.
In deep brain stimulation, surgery is performed to insert electrodes into a targeted area of the brain, using MRI and recordings of brain cell activity during the procedure. A second procedure is performed to implant an impulse generator or IPG (similar to a pacemaker) under the collarbone or in the abdomen. The IPG provides an electrical impulse to a part of the brain involved in motor function. Those who undergo DBS surgery are given a controller to turn the device on or off.
DBS is certainly the most important therapeutic advancement since the development of levodopa. It is most effective for individuals who experience disabling tremors, wearing-off spells and medication-induced dyskinesias, with studies showing benefits lasting at least five years. That said, it is not a cure and it does not slow PD progression. It is also not right for every person with PD.
Like all brain surgeries, DBS carries a small risk of infection, stroke, bleeding or seizures. DBS surgery may be associated with reduced clarity of speech. A small number of people with PD have experienced cognitive decline after DBS surgery.
It is very important that a person with PD who is thinking of DBS surgery be informed about the procedure and realistic in his or her expectations.
Carbidopa/levodopa enteral suspension (Duopa™) is a gel formulation of the gold-standard drug used to treat the motor symptoms of Parkinson’s. It is indicated for the treatment of motor fluctuations in advanced Parkinson’s.
The drug is delivered to the small intestine through a tube in the stomach. Surgery is required to place a small hole in the stomach that allows for drug delivery.
DUOPA™ uses the same active ingredients as orally-administered carbidopa/levodopa, but is designed to improve absorption and reduce off-times by delivering the drug directly to the small intestine.
Like any surgery, the procedure carries risks, as does use of the device that delivers the drug. These include movement or dislocation of the tube, infection, redness at the insertion point, pancreatitis, bleeding into the intestines, air or infection in the abdominal cavity, and failure of the pump. The drug may also lead to side effects. The drug is contraindicated for those taking nonselective monoamine oxidase (MAO) inhibitors.
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