Parkinson's disease is a slowly progressive degenerative disorder of the central nervous system. It is characterized by tremor when muscles are at rest (resting tremor), increased muscle tone (rigidity), slowness of voluntary movements, and difficulty maintaining balance (postural instability). Many people develop dementia.

• Parkinson's disease results from degeneration in the part of the brain that helps coordinate movements.
• Usually, the most obvious symptom is tremors that occur when muscles are relaxed.
• Muscles become stiff, movements become slow and uncoordinated, and balance is easily lost.
• Doctors base the diagnosis on symptoms.
• Changes in lifestyle, drugs (such as levodopa plus carbidopa), and sometimes surgery help lessen symptoms, but the disease is progressive, eventually causing severe disability and immobility.

Parkinson's disease affects about 1 of 250 people older than 40, about 1 of 100 people older than 65, and about 1 of 10 people older than 80. It commonly begins between the ages of 50 and 79. Rarely, Parkinson's disease occurs in children or adolescents.

When the brain initiates an impulse to move a muscle (for example, to lift an arm), the impulse passes through the basal ganglia (collections of nerve cells located deep within the brain). The basal ganglia help smooth out muscle movements and coordinate changes in posture. Like all nerve cells, those in the basal ganglia release chemical messengers (neurotransmitters) that trigger the next nerve cell in the pathway to send an impulse. A key neurotransmitter in the basal ganglia is dopamine. Its overall effect is to increase nerve impulses to muscles. In Parkinson's disease, nerve cells in part of the basal ganglia (called the substantia nigra) degenerate, reducing the production of dopamine and the number of connections between nerve cells in the basal ganglia. As a result, the basal ganglia cannot smooth out movements as they normally do, leading to tremor, loss of coordination, slow movement (bradykinesia), and a tendency to move less (hypokinesia).

What causes Parkinson's disease is unclear. According to one theory, Parkinson's disease may result from abnormal deposits of synuclein (a protein in the brain that helps nerve cells communicate). These deposits, called Lewy bodies, can accumulate in several regions of the brain, particularly in the substantia nigra (deep within the cerebrum) and interfere with brain function. Lewy bodies often accumulate in other parts of the brain and nervous system, suggesting that they may be involved in other disorders. In Lewy body dementia, Lewy bodies form throughout the outer layer of the brain (cerebral cortex). Lewy bodies may also be involved in Alzheimer's disease.

About 15 to 20% of affected people have relatives who have had Parkinson's disease. Thus, genetics may play a role.

Parkinsonism refers to symptoms of Parkinson's disease (such as slow movements and tremors) when they are caused by another condition. Various conditions can cause parkinsonism (see Movement Disorders: Parkinsonism).

Did You Know... Symptoms of Parkinson's disease can be caused by many other disorders and drugs. Parkinson's disease is sometimes hard to diagnose in older people because aging causes some of the same symptoms. Early in Parkinson's disease, delaying levodopa (the most useful treatment) is sometimes the best approach.

Symptoms

Usually, Parkinson's disease begins subtly and progresses gradually. In about two thirds of people, tremors are the first symptom. In others, the first symptom is usually problems with movement or a reduced sense of smell.

Parkinson's disease typically causes the following symptoms:

• Tremors: Tremors are coarse and rhythmic. They usually occur in one hand while the hand is at rest (a resting tremor). The tremor is called a pill-rolling tremor because the hand moves as if it is rolling small objects around. The tremor decreases when the hand is moving purposefully and disappears completely during sleep. Emotional stress or fatigue may worsen the tremor. The tremor may eventually progress to the other hand, the arms, and the legs. A tremor may also affect the jaws, tongue, forehead, and eyelids, but not the voice. In some people, a tremor never develops.
• Stiffness (rigidity): Muscles become stiff, impairing movement. When the forearm is bent back or straightened out by another person, the movement may feel stiff and ratchet-like (called cogwheel rigidity).
• Slowed movements: Movements become slow and difficult to initiate, and people tend to move less. Thus, mobility decreases.
• Difficulty maintaining balance and posture: Posture becomes stooped, and balance is difficult to maintain, leading to a tendency to fall forward or backward. Because movements are slow, people often cannot move their hands quickly enough to break a fall.

Walking becomes difficult, especially taking the first step. Once started, people often shuffle, taking short steps, keeping their arms bent at the waist, and not swinging their arms. While walking, some people have difficulty stopping or turning. When the disease is advanced, some people suddenly stop walking because they feel as if their feet are glued to the ground (called freezing). Other people unintentionally and gradually quicken their steps, breaking into a stumbling run to avoid falling. This symptom is called festination.

Stiffness and decreased mobility can contribute to muscle ache and fatigue. Because the small muscles of the hands are often impaired, daily tasks, such as buttoning a shirt and tying shoelaces, become increasingly difficult. Most people with Parkinson's disease have shaky, tiny handwriting (micrographia) because initiating and sustaining each stroke of the pen is difficult. Sensation and strength are usually normal.

The face becomes less expressive (masklike) because the facial muscles that control expression do not move. This lack of expression may be mistaken for depression, or it may cause depression to be overlooked. (Depression is common among people with Parkinson's disease.) Eventually, the face can take on a blank stare with the mouth open, and the eyes may not blink often. Often, people drool or choke because muscle rigidity in the face and throat makes swallowing difficult. People with Parkinson's disease often speak softly in a monotone and may stutter because they have difficulty articulating words.

Parkinson's disease also causes other symptoms:

• Insomnia is common, often because people need to urinate frequently or because symptoms worsen during the night, making turning over in bed difficult. Rapid-eye-movement (REM) sleep behavior disorder commonly develops. In this disorder, the limbs, which normally do not move in REM sleep, may move suddenly and violently, sometimes injuring a sleep partner. Lack of sleep may contribute to depression and drowsiness during the day.
• Urination may be difficult to start and to maintain (called urinary hesitancy).
• Constipation can develop because the intestine may move its contents more slowly. Inactivity and levodopa, the main drug used to treat Parkinson's disease, can worsen constipation.
• A sudden, excessive decrease in blood pressure may occur when a person stands up (orthostatic hypotension).
• Scales (seborrheic dermatitis) develop often on the scalp and face and occasionally in other areas.
• Dementia develops in about half the people with Parkinson's disease. In many people, intellect remains normal.

Diagnosis

The diagnosis is likely if the person has fewer, slow movements and either the characteristic tremor or muscle rigidity. Mild, early disease may be difficult for doctors to diagnose because it usually begins subtly. Diagnosis is especially difficult in older people because aging can cause some of the same problems as Parkinson's disease, such as loss of balance, slow movements, muscle stiffness, and stooped posture. To exclude other causes of the symptoms, doctors ask about previous disorders, exposure to toxins, and use of drugs that could cause parkinsonism.

No tests or imaging procedures can directly confirm the diagnosis. However, computed tomography (CT) and magnetic resonance imaging (MRI) may be done to look for a structural disorder that may be causing the symptoms. Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) can detect brain abnormalities typical of the disease. However, SPECT and PET are currently used only in research facilities.

If the diagnosis is unclear, doctors may give the person levodopa, a drug used to treat Parkinson's disease. If levodopa results in clear improvement, Parkinson's disease is likely.

Treatment

General measures used to treat Parkinson's disease can help people function. Many drugs (such as levodopa-carbidopa) can make movement easier and enable people with Parkinson's disease to function effectively for many years. But no drug can cure the disease. Two or more drugs may be needed. For older people, doses are often reduced. Drugs that cause or worsen symptoms, particularly antipsychotics, are avoided. If the disease is advanced and drugs are ineffective or cause severe side effects, surgery is considered.

General Measures: Various simple measures can help people with Parkinson's disease maintain mobility and independence:

• Continuing to do as many daily activities as possible
• Following a program of regular exercise
• Simplifying daily tasks—for example having buttons on clothing replaced with Velcro fasteners or buying shoes with Velcro fasteners
• Using assistive devices, such as zipper pulls and button hooks

Physical therapists (see Rehabilitation: Physical Therapy (PT)) and occupational therapists (see see Rehabilitation: Occupational Therapy (OT)) can help people learn how to incorporate these measures into their daily activities, as well as recommend exercises to improve muscle tone and maintain range of motion. Therapists may also recommend mechanical aids, such as wheeled walkers, to help people maintain independence.

Simple changes around the home can make it safer for people with Parkinson's disease:

• Removing throw rugs to prevent tripping
• Installing grab bars in bathrooms and railings in hallways and other locations to reduce the risk of falling

For constipation, the following can help:

• Consuming a high-fiber diet, including such foods as prunes and fruit juices
• Exercising
• Drinking plenty of fluids
• Using stool softeners (such as senna concentrate), supplements (such as psyllium), or stimulant laxatives (such as bisacodyl taken by mouth) to keep bowel movements regular

Difficulty swallowing may limit food intake, so the diet must be nutritious. Making an effort to sniff more deeply may improve the ability to smell, enhancing the appetite.

Levodopa-Carbidopa: Traditionally, levodopa, which is given with carbidopa, is the first drug used. These drugs, taken by mouth, are the mainstay of treatment for Parkinson's disease. However, some experts think that using levodopa early in the disease may cause side effects to develop more quickly, and people may stop responding to the drug sooner. Thus, a drug with anticholinergic effects, amantadine, or a drug that mimics the action of dopamine (a dopamine agonist) may be used first.

Levodopa reduces muscle rigidity, improves movement, and substantially reduces tremor. Taking levodopa produces dramatic improvement in people with Parkinson's disease. The drug enables many people with mild disease to return to a nearly normal level of activity and enables some people who are confined to bed to walk again. However, levodopa usually does not help people with parkinsonism (which is due to another disorder).

Levodopa is a dopamine precursor, which means that the body can convert it to dopamine. Conversion may occur in the basal ganglia, thus compensating for the decrease in dopamine production. But levodopa can also be converted to dopamine early, on its way to the brain. When levodopa is converted early, the amount of dopamine available for controlling symptoms is reduced. Also, dopamine levels in the blood increase, increasing the risk of side effects such as nausea and flushing. Giving carbidopa with levodopa prevents this early conversion of levodopa. When the two drugs are given together, a lower dose of levodopa can be used, and nausea and flushing occur less often and are less severe.

To determine the best dose of levodopa for a particular person, doctors must balance control of the disease with the development of certain side effects, which may limit the amount of levodopa the person can tolerate. These side effects include involuntary movements (of the mouth, face, and limbs), nightmares, hallucinations, and changes in blood pressure.

After taking levodopa for 5 or more years, more than half the people begin to alternate rapidly between a good response to the drug and no response—an effect called the on-off phenomenon. Within seconds, they may change from being fairly mobile to being severely impaired and immobile. The periods of mobility after each dose become shorter and may be accompanied by involuntary movements (dyskinesias) due to levodopa use, including writhing or hyperactivity. Taking lower, more frequent doses controls these effects for a while. Other options are switching to a controlled-release formulation or adding a dopamine agonist or amantadine. However, after 15 to 20 years, these effects become hard to suppress. Surgery is then considered.

Other Drugs: Other drugs are generally less effective than levodopa, but they may benefit some people, particularly if levodopa is not tolerated or is insufficient.

Dopamine agonists (such as pramipexole and ropinirole), which mimic the action of dopamine, may be useful at any stage of the disease. Another dopamine agonist, rotigotine, is available as a skin patch. Apomorphine, a quick-acting dopamine agonist injected under the skin (subcutaneously), is used to reverse the off part of levodopa's on-off phenomenon—when movement is difficult to initiate. Thus, this drug is called rescue therapy. It is usually used when people freeze in place, preventing them, for example, from walking. Affected people or another person (such as a family member) can inject the drug up to 5 times a day as needed.

Rasagiline and selegiline belong to a class of drugs called monoamine oxidase inhibitors (MAO inhibitors—see Mood Disorders: Drugs Used to Treat Depression). They prevent the breakdown of dopamine, thereby prolonging dopamine's action in the body. If taken with certain foods (such as certain cheeses), beverages (such as red wine), or drugs, MAO inhibitors can have a serious side effect called hypertensive crisis (see Factors Affecting Response to Drugs: Some Drug-Food Interactions). However, this effect is unlikely when Parkinson's disease is being treated because the doses used are low and the type of MAO inhibitor used (MAO type B inhibitors) is less likely to have this effect.

Entacapone prevents the breakdown of dopamine and appears to be a useful supplement to levodopa. Tolcapone works similarly to entacapone but is rarely used because it can damage the liver.

Some drugs with anticholinergic effects (see Aging and Drugs: Anticholinergic: What Does It Mean?), such as benztropine and trihexyphenidyl, are effective in reducing the severity of a tremor and can be used in the early stages of Parkinson's disease. They can also be used in the later stages to supplement levodopa. These drugs may reduce tremor because they block the action of acetylcholine, and tremor is thought to be caused by an imbalance of acetylcholine (too much) and dopamine (too little). Other drugs with anticholinergic effects, including some antihistamines and tricyclic antidepressants, are mildly effective and may be used to supplement levodopa. However, many anticholinergic effects are troublesome, especially in older people. These effects include confusion, drowsiness, dry mouth, blurred vision, dizziness, constipation, difficulty urinating, and loss of bladder control.

Amantadine, a drug sometimes used to treat influenza, may be used alone to treat mild Parkinson's disease or as a supplement to levodopa. Amantadine probably has many effects that make it work. For example, it probably stimulates nerve cells to release dopamine.

Propranolol, a beta-blocker, may be used to reduce the severity of a tremor.

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Drugs Used to Treat Parkinson's Disease Drug Some Side Effects Comments Dopamine precursor Levodopa (given with carbidopa) For levodopa: Involuntary movements (of the mouth, face, and limbs), nightmares, low blood pressure when a person stands up (orthostatic hypotension), constipation, nausea, drowsiness, confusion, hallucinations, palpitations, and flushing If these drugs are suddenly stopped, neuroleptic malignant syndrome (with high fever, high blood pressure, rigidity, muscle damage, and coma), which can be life threatening This combination is the mainstay of treatment. Carbidopa helps increase the effectiveness of levodopa and reduce its side effects. After several years, the effectiveness of the combination may lessen. Dopamine agonists Bromocriptine Pramipexole Ropinirole Drowsiness, nausea, orthostatic hypotension, involuntary movements, confusion, and hallucinations When these drugs are suddenly stopped, neuroleptic malignant syndrome Early in the disease, these drugs may be used alone or with small doses of levodopa to possibly delay levodopa's side effects. Later in the disease, dopamine agonists are useful when the on-off effects of levodopa make it less effective. Apomorphine Severe nausea, vomiting, and lumps (nodules) under the skin at the injection site This quick-acting drug is injected under the skin. It is used as rescue therapy to reverse the off effect of levodopa. Rotigotine Drowsiness, nausea, orthostatic hypotension, confusion, hallucinations, weight gain (possibly due to fluid retention), and sometimes irritation at the application site This drug is available as a skin patch. It is used alone early in the disease. The patch is worn continuously for 24 hours, then removed and replaced. The patch should be placed in different locations each day to reduce the risk of skin irritation. MAO-B inhibitors Rasagiline Nausea, insomnia, drowsiness, and swelling due to fluid accumulation (edema) If people take doses that are higher than those usually used to treat Parkinson's disease and consume foods or beverages that contain tyramine (such as certain cheeses and red wine) or take certain other drugs, hypertensive crisis (a severe headache and a potentially fatal increase in blood pressure) Rasagiline can be used alone to postpone the use of levodopa but is often given as a supplement to levodopa. At best, rasagiline is modestly effective. Selegiline Worsening of nausea, confusion, and involuntary movements due to levodopa Selegiline can be used alone to postpone the use of levodopa but is often given as a supplement to levodopa. At best, selegiline is modestly effective. COMT inhibitors Entacapone Tolcapone Nausea, involuntary movements, confusion, diarrhea, back pain, and discoloration of the urine These drugs can be used to supplement levodopa late in the disease and to extend the interval between doses of levodopa. Anticholinergic drugs Benztropine Trihexyphenidyl Tricyclic antidepressants (such as amitriptyline), used if depression also needs to be treated Some antihistamines (such as diphenhydramine) Drowsiness, confusion, dry mouth, blurred vision, dizziness, constipation, difficulty urinating, loss of bladder control, and impaired regulation of body temperature These drugs may be given alone in the early stages of the disease or as a supplement to levodopa in the later stages. They can reduce tremor but do not affect slow movements or muscle rigidity. Antiviral drug Amantadine Nausea, dizziness, insomnia, anxiety, confusion, edema, difficulty urinating, worsening of glaucoma, and mottled discoloration of the skin due to dilated blood vessels (livedo reticularis) Rarely, when the drug is stopped or the dose is reduced, neuroleptic malignant syndrome Amantadine is used alone in the early stages for mild disease but may become ineffective after several months. Later, it is used to supplement levodopa and to lessen involuntary movements due to levodopa. Beta-blocker Propranolol Spasm of the airways (bronchospasm), an abnormally slow heart rate (bradycardia), heart failure, possible masking of low blood sugar levels after insulin injections, impaired peripheral circulation, insomnia, fatigue, shortness of breath, depression, Raynaud's phenomenon, vivid dreams, hallucinations, and sexual dysfunction Propranolol can be used to reduce the severity of tremors. MAO-B = monoamine oxidase type B; COMT = catechol O-methyltransferase. Drugs Used to Treat Parkinson's Disease Drug Some Side Effects Comments Dopamine precursor Levodopa (given with carbidopa) For levodopa: Involuntary movements (of the mouth, face, and limbs), nightmares, low blood pressure when a person stands up (orthostatic hypotension), constipation, nausea, drowsiness, confusion, hallucinations, palpitations, and flushing If these drugs are suddenly stopped, neuroleptic malignant syndrome (with high fever, high blood pressure, rigidity, muscle damage, and coma), which can be life threatening This combination is the mainstay of treatment. Carbidopa helps increase the effectiveness of levodopa and reduce its side effects. After several years, the effectiveness of the combination may lessen. Dopamine agonists Bromocriptine Pramipexole Ropinirole Drowsiness, nausea, orthostatic hypotension, involuntary movements, confusion, and hallucinations When these drugs are suddenly stopped, neuroleptic malignant syndrome Early in the disease, these drugs may be used alone or with small doses of levodopa to possibly delay levodopa's side effects. Later in the disease, dopamine agonists are useful when the on-off effects of levodopa make it less effective. Apomorphine Severe nausea, vomiting, and lumps (nodules) under the skin at the injection site This quick-acting drug is injected under the skin. It is used as rescue therapy to reverse the off effect of levodopa. Rotigotine Drowsiness, nausea, orthostatic hypotension, confusion, hallucinations, weight gain (possibly due to fluid retention), and sometimes irritation at the application site This drug is available as a skin patch. It is used alone early in the disease. The patch is worn continuously for 24 hours, then removed and replaced. The patch should be placed in different locations each day to reduce the risk of skin irritation. MAO-B inhibitors Rasagiline Nausea, insomnia, drowsiness, and swelling due to fluid accumulation (edema) If people take doses that are higher than those usually used to treat Parkinson's disease and consume foods or beverages that contain tyramine (such as certain cheeses and red wine) or take certain other drugs, hypertensive crisis (a severe headache and a potentially fatal increase in blood pressure) Rasagiline can be used alone to postpone the use of levodopa but is often given as a supplement to levodopa. At best, rasagiline is modestly effective. Selegiline Worsening of nausea, confusion, and involuntary movements due to levodopa Selegiline can be used alone to postpone the use of levodopa but is often given as a supplement to levodopa. At best, selegiline is modestly effective. COMT inhibitors Entacapone Tolcapone Nausea, involuntary movements, confusion, diarrhea, back pain, and discoloration of the urine These drugs can be used to supplement levodopa late in the disease and to extend the interval between doses of levodopa. Anticholinergic drugs Benztropine Trihexyphenidyl Tricyclic antidepressants (such as amitriptyline), used if depression also needs to be treated Some antihistamines (such as diphenhydramine) Drowsiness, confusion, dry mouth, blurred vision, dizziness, constipation, difficulty urinating, loss of bladder control, and impaired regulation of body temperature These drugs may be given alone in the early stages of the disease or as a supplement to levodopa in the later stages. They can reduce tremor but do not affect slow movements or muscle rigidity. Antiviral drug Amantadine Nausea, dizziness, insomnia, anxiety, confusion, edema, difficulty urinating, worsening of glaucoma, and mottled discoloration of the skin due to dilated blood vessels (livedo reticularis) Rarely, when the drug is stopped or the dose is reduced, neuroleptic malignant syndrome Amantadine is used alone in the early stages for mild disease but may become ineffective after several months. Later, it is used to supplement levodopa and to lessen involuntary movements due to levodopa. Beta-blocker Propranolol Spasm of the airways (bronchospasm), an abnormally slow heart rate (bradycardia), heart failure, possible masking of low blood sugar levels after insulin injections, impaired peripheral circulation, insomnia, fatigue, shortness of breath, depression, Raynaud's phenomenon, vivid dreams, hallucinations, and sexual dysfunction Propranolol can be used to reduce the severity of tremors. MAO-B = monoamine oxidase type B; COMT = catechol O-methyltransferase.

Deep Brain Stimulation: People with involuntary movements due to long-term use of levodopa may benefit from deep brain stimulation. Tiny electrodes are surgically implanted in part of the basal ganglia. By stimulating this part, deep brain stimulation often greatly reduces the involuntary movements and tremors and shortens the off part of the on-off phenomenon.

Stem Cells: Transplantation of stem cells to treat Parkinson's disease has received much publicity. Theoretically, stem cells, such as those derived from bone marrow or embryos, could be transplanted into the brain and become capable of producing dopamine. However, studies to determine whether this treatment is effective and safe in people will take many years.

Caregiver and End-of-Life Issues: Because Parkinson's disease is progressive, people eventually need help with normal daily activities, such as eating, bathing, dressing, and toileting. Caregivers can benefit from learning about the physical and psychologic effects of Parkinson's disease and about ways to enable people to function as well as possible. Because such care is tiring and stressful, caregivers may benefit from support groups.

Eventually, most people with Parkinson's disease become severely disabled and immobile. They may be unable to eat, even with assistance. Dementia develops in about half the people. Because swallowing becomes increasingly difficult, death due to aspiration pneumonia is a risk. For some people, a nursing home may be the best place for care. Before people with this disease are incapacitated, they should establish advance directives, indicating what kind of medical care they want at the end of life (see Death and Dying: Dry Mouth).

Last full review/revision August 2007 by David Eidelberg, MD; Michael Pourfar, MD