What is Parkinson's disease?

Parkinson's disease is the second most common neurodegenerative disorder and the most common movement disorder. It is characterized by progressive loss of muscle control, which leads to trembling of the limbs and head while at rest, stiffness, slowness, and impaired balance. As symptoms worsen, it may become difficult to walk, talk, and complete simple tasks.
The progression of Parkinson's disease and the degree of impairment vary from individual to individual. Many people with Parkinson's disease live long productive lives, whereas others become disabled much more quickly. Premature death is usually due to complications such as falling-related injuries or pneumonia.
In the United States, about 1 million people are affected by Parkinson's disease and worldwide about 5 million. Most individuals who develop Parkinson's disease are 60 years of age or older. Parkinson's disease occurs in approximately 1% of individuals aged 60 years and in about 4% of those aged 80 years. Since overall life expectancy is rising, the number of individuals with Parkinson's disease will increase in the future. Adult-onset Parkinson's disease is most common, but early-onset Parkinson's disease (onset between 21-40 years), and juvenile-onset Parkinson's disease (onset before age 21) also exist.
Descriptions of Parkinson's disease date back as far as 5000 BC. Around that time, an ancient Indian civilization called the disorder Kampavata and treated it with the seeds of a plant containing therapeutic levels of what is today known as levodopa. Parkinson's disease was named after the British doctor James Parkinson, who in 1817 first described the disorder in great detail as "shaking palsy."

Sign & Symptoms

The symptoms of Parkinson's disease can vary from person to person. Early signs may be subtle and can go unnoticed. Symptoms typically begin on one side of the body and usually remain worse on that side even after symptoms begin to affect both sides. Parkinson's signs and symptoms may include:

Tremor. The characteristic shaking associated with Parkinson's disease often begins in a hand. A back-and-forth rubbing of your thumb and forefinger, known as pill-rolling, is common, and may occur when your hand is at rest. However, not everyone experiences tremors.
Slowed motion (bradykinesia). Over time, Parkinson's disease may reduce your ability to initiate voluntary movement. This may make even the simplest tasks difficult and time-consuming. When you walk, your steps may become short and shuffling. Or your feet may freeze to the floor, making it hard to take the first step.
Rigid muscles. Muscle stiffness can occur in any part of your body. Sometimes the stiffness can be so severe that it limits the range of your movements and causes pain. People may first notice this sign when you no longer swing your arms when you're walking.
Impaired posture and balance. Your posture may become stooped as a result of Parkinson's disease. Balance problems also may occur, although this is usually in the later stages of the disease.
Loss of automatic movements. Blinking, smiling and swinging your arms when you walk are all unconscious acts that are a normal part of being human. In Parkinson's disease, these acts tend to be diminished and even lost. Some people may develop a fixed staring expression and unblinking eyes. Others may no longer gesture or seem animated when they speak.
Speech changes. Many people with Parkinson's disease have problems with speech. You may speak more softly, rapidly or in a monotone, sometimes slurring or repeating words, or hesitating before speaking.
Dementia. In the later stages of Parkinson's disease, some people develop problems with memory and mental clarity. Alzheimer's drugs appear to alleviate some of these symptoms to a mild degree.

What causes Parkinson's disease?

A substance called dopamine acts as a messenger between two brain areas - the substantia nigra and the corpus striatum - to produce smooth, controlled movements. Most of the movement-related symptoms of Parkinson's disease are caused by a lack of dopamine due to the loss of dopamine-producing cells in the substantia nigra. When the amount of dopamine is too low, communication between the substantia nigra and corpus striatum becomes ineffective, and movement becomes impaired; the greater the loss of dopamine, the worse the movement-related symptoms. Other cells in the brain also degenerate to some degree and may contribute to non-movement related symptoms of Parkinson's disease.
Although it is well known that lack of dopamine causes the motor symptoms of Parkinson's disease, it is not clear why the dopamine-producing brain cells deteriorate. Genetic and pathological studies have revealed that various dysfunctional cellular processes, inflammation, and stress can all contribute to cell damage. In addition, abnormal clumps called Lewy bodies, which contain the protein alpha-synuclein, are found in many brain cells of individuals with Parkinson's disease. The function of these clumps in regards to Parkinson's disease is not understood. In general, scientists suspect that dopamine loss is due to a combination of genetic and environmental factors.

Tests and Investigation

No definitive tests exist for Parkinson's disease, so it can be difficult to diagnose, especially in the early stages. And parkinsonism — the symptoms of Parkinson's disease — can be caused by many other types of problems. For example, other neurological disorders, toxins, head trauma and even some medications — such as chlorpromazine (Thorazine), prochlorperazine (Compazine) or metoclopramide (Reglan) — can cause parkinsonism.
A diagnosis of Parkinson's disease is based on your medical history and a neurological examination:

Medical history. As part of your medical history, your doctor will want to know about any medications you take and whether you have a family history of Parkinson's.
Neurological exam. This examination includes an evaluation of your walking and coordination, as well as some simple hand tasks.

A diagnosis of Parkinson's is most likely if you have:

At least two of the three cardinal Parkinson's signs and symptoms — tremor, slowing of motion and muscle rigidity
Onset of symptoms on only one side of the body
Tremor more pronounced at rest, for example, when your hands are resting in your lap
Significant improvement with levodopa, a Parkinson's drug

What is the prognosis of Parkinson's disease?

The severity of Parkinson's disease symptoms vary greatly from individual to individual and it is not possible to predict how quickly the disorder will progress. Parkinson's disease itself is not a fatal disease, and the average life expectancy is similar to that of people without the disease. Secondary complications, such as pneumonia, falling-related injuries, and choking can lead to death. There are many treatment options that can reduce some of the symptoms and can prolong the quality of life of an individual with Parkinson's disease.

Treatments and Pharmacology

There's no cure for Parkinson's disease, but medications can help control some of the symptoms of Parkinson's disease, and in some case, surgery may be helpful. Your doctor may recommend lifestyle changes, such as physical therapy, a healthy diet and exercise, in addition to medications.
Medications
Medications can help manage problems with walking, movement and tremor by increasing the brain's supply of dopamine. However, taking dopamine itself is not helpful, because it's unable to enter your brain.
Your initial response to Parkinson's treatment can be dramatic. Over time, however, the benefits of drugs frequently diminish or become less consistent, although symptoms can usually still be fairly well controlled.
Examples of medication your doctor may prescribe include:

Levodopa. The most effective Parkinson's drug is levodopa, which is a natural substance in the body. When taken by mouth in pill form, it passes into the brain and is converted to dopamine. Levodopa is combined with carbidopa to create the combination drug, Sinemet. The carbidopa protects levodopa from premature conversion to dopamine outside the brain; in doing that, it also prevents nausea. In Europe, levodopa is combined with a similar substance, benserazide, and is marketed as Madopar.
As the disease progresses, the benefit from levodopa may become less stable, with a tendency to wax and wane ("wearing off"). This then requires medication adjustments. Levodopa side effects include involuntary movements called dyskinesia. These resolve with dose reduction, but sometimes at the expense of reduced parkinsonism control. Like other Parkinson's drugs, it may also lower your blood pressure when standing.
Dopamine agonists. Unlike levodopa, these drugs aren't changed into dopamine. Instead, they mimic the effects of dopamine in the brain and cause neurons to react as though dopamine is present. They are not nearly as effective in treating the symptoms of Parkinson's disease. However, they last longer and are often used to smooth the sometimes off-and-on effect of levodopa.
This class includes pill forms of dopamine agonists, such as pramipexole (Mirapex) and ropinirole (Requip). A short-acting injectable dopamine agonist, apomorphine (Apokyn), is used for quick relief.
The side effects of dopamine agonists include hallucinations, sleepiness, water retention and low blood pressure when standing. These medications may also increase your risk of compulsive behaviors such as hypersexuality, compulsive gambling and compulsive overeating. If you are taking these medications and start behaving in a way that's out of character for you, talk to your doctor.
MAO B inhibitors. These types of drugs, including selegiline (Eldepryl) and rasagiline (Azilect), help prevent the breakdown of both naturally occurring dopamine and dopamine formed from levodopa. They do this by inhibiting the activity of the enzyme monoamine oxidase B (MAO B) — an enzyme that metabolizes dopamine in the brain. Side effects are rare but may include confusion, headache, hallucinations and dizziness. These medications can't be used in combination with other antidepressants, the antibiotic ciprofloxacin (Cipro), the herb St. John's wort or certain narcotics. Check with your doctor before taking any additional medications with an MAO inhibitor.
Catechol O-methyltransferase (COMT) inhibitors. These drugs prolong the effect of carbidopa-levodopa therapy by blocking an enzyme that breaks down levodopa. Tolcapone (Tasmar) has been linked to liver damage and liver failure, so it's normally used only in people who aren't responding to other therapies. Entacapone (Comtan) doesn't cause liver problems and is now combined with carbidopa and levodopa in a medication called Stalevo. However, it may worsen other levodopa side effects, such as involuntary movements (dyskinesias), nausea, confusion or hallucinations. It may cause urine discoloration.
Anticholinergics. These drugs have been used for many years to help control the tremor associated with Parkinson's disease. A number of anticholinergic drugs, such as benztropine (Cogentin) and trihexyphenidyl, are available. However, their modest benefits are often offset by side effects such as impaired memory, confusion, constipation, dry mouth and eyes, and impaired urination.
Glutamate (NMDA) blocking drugs. Doctors may prescribe amantadine (Symmetrel) alone to provide short-term relief of mild, early-stage Parkinson's disease. It also may be added to carbidopa-levodopa therapy for people in the later stages of Parkinson's disease, especially if they have problems with involuntary movements (dyskinesia) induced by carbidopa-levodopa. Side effects include a purple mottling of the skin and, sometimes, hallucinations.

Physical therapy
Exercise is important for general health, but especially for maintaining function in Parkinson's disease. Physical therapy may be advisable and can help improve your mobility, range of motion and muscle tone. Although specific exercises can't stop the progress of the disease, maintaining muscle strength and agility can help counter some of the progressive tendencies of the disease and also allow you to feel more confident and capable. A physical therapist can also work with you to improve your gait and balance. A speech therapist or speech pathologist can improve problems with speaking and swallowing.
Surgery
Deep brain stimulation is a surgical procedure used to treat Parkinson's disease. It involves implanting an electrode deep within the parts of your brain that control movement. The amount of stimulation delivered by the electrode is controlled by a pacemaker-like device placed under the skin in your upper chest. A wire that travels under your skin connects the device, called a pulse generator, to the electrodes.
Deep brain stimulation is most often used for people with advanced Parkinson's disease who have unstable medication (levodopa) responses. It can stabilize medication fluctuations and reduce or eliminate involuntary movements (dyskinesia). Tremor is especially responsive to this therapy.
Serious risks of this procedure are uncommon, but include brain hemorrhage or stroke. Infection is also a risk, and sometimes requires parts of the device to be replaced. Deep brain stimulation isn't beneficial for people who don't respond to carbidopa-levodopa.

REFERENCES:

Arenas, E. Towards stem cell replacement therapies for Parkinson's disease. Biochemical and Biophysical Research Communications, 2010; vol 396: pp 152-156.

Chen, J.C. Parkinson's Disease: Health-Related Quality of Life, Economic Cost, and Implications of Early Treatment American Journal of Managing Care, 2010; vol 16: pp S87-S93.

Fricker-Gates, R.A. and Gates, M.A. Stem cell-derived dopamine neurons for repair in Parkinson's disease. Regenerative Medicine, March 2010; vol 5(2): pp267-78.

Hauser, R.A., Early Pharmacologic Treatment in Parkinson's Disease. American Journal of Managing Care, 2010; vol 16: pp S100-S107.

Pahwa, R. and Lyons, K.E. diagnosis of Parkinson's disease: recommendations from diagnostic clinical guidelines. American Journal of Managing Care, 2010; vol 16: pp S194-S99.