* This is the Consumer Version. *
- Changes inside the brain
- More Information
- Resources In This Article
- Drugs Mentioned In This Article
Parkinson Disease (PD)
Parkinson disease is a slowly progressive degenerative disorder of specific areas of the central nervous system (brain and spinal cord). It is characterized by tremor when muscles are at rest (resting tremor), increased muscle tone (stiffness, or rigidity), slowness of voluntary movements, and difficulty maintaining balance (postural instability). In many people, thinking becomes impaired, or dementia develops.
Parkinson disease results from degeneration in the part of the brain that helps coordinate movements.
Often, 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.
General measures (such as simplifying daily tasks), drugs (such as levodopa plus carbidopa), and sometimes surgery can help, but the disease is progressive, eventually causing severe disability and immobility.
Parkinson disease is the second most common degenerative disorder of the central nervous system after Alzheimer disease. It affects
It commonly begins between the ages of 50 and 79. Rarely, Parkinson disease occurs in children or adolescents.
Parkinsonism causes the same symptoms as Parkinson disease but is caused by various other conditions, such as multiple system atrophy, progressive supranuclear palsy, stroke, head injury, or certain drugs.
In Parkinson disease, nerve cells in part of the basal ganglia (called the substantia nigra) degenerate.
The basal ganglia are collections of nerve cells located deep within the brain. They help smooth out muscle movements and coordinate changes in posture. When the brain initiates an impulse to move a muscle (for example, to lift an arm), the impulse passes through the basal ganglia. 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.
When nerve cells in the basal ganglia degenerate, they produce less dopamine, and the number of connections between nerve cells in the basal ganglia decreases. As a result, the basal ganglia cannot smooth out movements as they normally do, leading to tremor, loss of coordination, slow movement (bradykinesia), a tendency to move less (hypokinesia), and problems with posture and walking.
Locating the Basal Ganglia
The basal ganglia are collections of nerve cells located deep within the brain. They include the following:
The basal ganglia help smooth out muscle movements and coordinate changes in posture.
What causes Parkinson disease is unclear. According to one theory, Parkinson 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 disease, possibly explaining why about one third of people with Parkinson disease have symptoms of Alzheimer disease and why some people with Alzheimer disease develop parkinsonian symptoms.
About 15 to 20% of people with Parkinson disease have relatives who have or have had the disease. Thus, genetics may play a role.
Usually, Parkinson disease begins subtly and progresses gradually.
The first symptom is
Tremors typically have the following characteristics:
Are coarse and rhythmic
Usually occur in one hand while the hand is at rest (a resting tremor)
Often involve the hand moving as if it is rolling small objects around (called pill-rolling)
Decrease when the hand is moving purposefully and disappear completely during sleep
May be worsened by emotional stress or fatigue
May eventually progress to the other hand, the arms, and the legs
May also affect the jaws, tongue, forehead, and eyelids, but not the voice
In some people, a tremor never develops.
Parkinson disease typically also causes the following symptoms:
Stiffness (rigidity): Muscles become stiff, making movement difficult. When a doctor tries to bend the person's forearm back or straighten it out, the arm resists being moved and, when it moves, moves it starts and stops, as it is being ratcheted (called cogwheel rigidity).
Slowed movements: Movements become slow and difficult to initiate, and people tend to move less. When they move less, moving becomes more difficult because joints become stiff and muscles weaken.
Difficulty maintaining balance and posture: Posture becomes stooped, and balance is difficult to maintain. Thus, people tend to topple 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 swinging their arms little or not at all. 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. Having stiff muscles interferes with many movements: turning over in bed, getting in or out of a car, and standing up from a deep chair. Usual daily tasks (such as dressing, combing the hair, eating, and brushing the teeth) take longer.
Because people often have difficulty controlling the small muscles of the hands, daily tasks, such as buttoning a shirt and tying shoelaces, become increasingly difficult. Most people with Parkinson disease have shaky, tiny handwriting (micrographia) because initiating and sustaining each stroke of the pen is difficult. People may mistakenly think of these symptoms as weakness. However, strength and sensation are usually normal.
The face becomes less expressive (masklike) because the facial muscles that control expression do not move as much as they normally would. This lack of expression may be mistaken for depression, or it may cause depression to be overlooked. (Depression is common among people with Parkinson 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 the muscles in the face and throat are stiff, making swallowing difficult. People often speak softly in a monotone and may stutter because they have difficulty articulating words.
Parkinson disease also causes other symptoms:
Sleep problems, including insomnia, are 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 because people are acting out their dreams, sometimes injuring a bed partner. Lack of sleep may contribute to depression and drowsiness during the day.
Urination problems may occur. Urination may be difficult to start and to maintain (called urinary hesitancy). People may have a compelling need to urinate (urgency). Incontinence is common.
Constipation can develop because the intestine may move its contents more slowly. Inactivity and levodopa, the main drug used to treat Parkinson 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.
Loss of smell (anosmia) is common, but people may not notice it.
Dementiadevelops in about one third of people with Parkinson disease. In many others, thinking is impaired, but people may not recognize it.
Depressioncan develop, sometimes years before people have problems with movement. Depression tends to worsen as Parkinson disease becomes more severe. Depression can also make movement problems worse.
Hallucinations, delusions, and paranoia can occur, particularly if dementia develops. People may see or hear things that are not there (hallucinations) or firmly hold certain beliefs despite clear evidence that contradicts them (delusions). They may become mistrustful and think other people intend them harm (paranoia). These symptoms are considered psychotic symptoms because they represent loss of contact with reality. Psychotic symptoms are the most common reason people with Parkinson disease are put in an institution. Having these symptoms increases the risk of dying.
Mental symptoms, including psychotic symptoms, may be caused by Parkinson disease or by a drug used to treat it.
The drugs used to treat Parkinson disease (see Table: Drugs Used to Treat Parkinson Disease) can also cause problems, such as obsessive-compulsive behavior or difficulty controlling urges, resulting, for example, in compulsive gambling or collecting.
Parkinson disease is likely if people have the following:
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 disease, such as loss of balance, slow movements, muscle stiffness, and stooped posture. Sometimes essential tremor is misdiagnosed as Parkinson disease.
To exclude other causes of the symptoms, doctors ask about previous disorders, exposure to toxins, and use of drugs that could cause parkinsonism.
During the physical examination, doctors ask people to do certain movements, which can help establish the diagnosis. For example, in people with Parkinson disease, the tremor disappears or lessens when doctors ask them to touch their nose with their finger. Also, people with the disease have difficulty performing rapidly alternating movements, such as placing their hands on their thighs, then rapidly turning their hands over back and forth several times.
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 and do not distinguish Parkinson disease from other disorders that cause the same symptoms (parkinsonism).
If the diagnosis is unclear, doctors may give the person levodopa, a drug used to treat Parkinson disease. If levodopa results in clear improvement, Parkinson disease is likely.
General measures used to treat Parkinson disease can help people function better.
Many drugs can make movement easier and enable people to function effectively for many years. The mainstay of treatment for Parkinson disease is
Other drugs are generally less effective than levodopa, but they may benefit some people, particularly if levodopa is not tolerated or is inadequate. However, 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 antipsychotic drugs, are avoided.
The drugs used to treat Parkinson disease can have troublesome side effects. If people notice any unusual effects (such as difficulty controlling urges or confusion), they should report them to their doctor. They should not stop taking a drug unless their doctor tells them to.
Deep brain stimulation, a surgical procedure, is considered if people have advanced disease but no dementia nor psychiatric symptoms and drugs are ineffective or have severe side effects.
Various simple measures can help people with Parkinson disease maintain mobility and independence:
Physical therapists and occupational therapists 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 disease:
For constipation, the following can help:
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.
Traditionally, levodopa, which is given with carbidopa, is the first drug used. These drugs, taken by mouth, are the mainstay of treatment for Parkinson disease. But when taken for a long time, levodopa may have side effects and become less effective. So some experts have suggested that using other drugs first and delaying use of levodopa might help. However, evidence now indicates that the side effects and reduced effectiveness after long-term use probably occur because Parkinson disease is worsening and are not related to when the drug was begun. Still, because levodopa may become less effective after several years of use, doctors may prescribe another drug for people under 60, who will be taking drugs to treat the disease for a long time. Other drugs that may be used include amantadine and dopamine agonists (drugs that act like dopamine, stimulating the same receptors on brain cells). Such drugs are used because production of dopamine is decreased in Parkinson disease.
Levodopa reduces muscle stiffness, improves movement, and substantially reduces tremor. Taking levodopa produces dramatic improvement in people with Parkinson 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.
Levodopa is a dopamine precursor. That is, it is converted into dopamine in the body. Conversion occurs in the basal ganglia, where levodopa helps compensate for the decrease in dopamine due to the disease. However, before levodopa reaches the brain, some of it is converted to dopamine in the intestine and in the blood. Having dopamine in the intestine and blood increases the risk of side effects such as vomiting, orthostatic hypotension, and flushing. Carbidopa is given with levodopa to prevent levodopa from being converted to dopamine before it reaches the basal ganglia. As a result, there are fewer side effects, and more dopamine is available to the brain.
To determine the best dose of levodopa for a particular person, doctors must balance control of the disease with the development of side effects, which may limit the amount of levodopa the person can tolerate. These side effects include
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—called on-off effects. Within seconds, people may change from being fairly mobile to being severely impaired and immobile. The periods of mobility after each dose become shorter, and symptoms may occur before the next scheduled dose—the off effects. Also, symptoms may be accompanied by involuntary movements due to levodopa use, including writhing or hyperactivity. One of the following can be used to control the off effects for a while:
However, after 15 to 20 years, the off effects become hard to suppress. Surgery is then considered.
A formulation of levodopa/carbidopa (available in Europe) can be given using a pump connected to a feeding tube inserted in the small intestine. This formulation is being studied as treatment for people who have severe symptoms that cannot be relieved by drugs and who cannot undergo surgery. This formulation appears to greatly reduce the off times and increase quality of life.
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, which act like dopamine, may be useful at any stage of the disease. They include
Because apomorphine is quick-acting, it is used to reverse the off effects of levodopa—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. In some countries, apomorphine is available in a formulation that can be given using a pump to people who have severe symptoms when surgery is not an option.
Rasagiline and selegilinebelong to a class of drugs called monoamine oxidase inhibitors (MAO inhibitors). They prevent the breakdown of dopamine, thereby prolonging dopamine’s action in the body. Theoretically, 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. However, this effect is unlikely when Parkinson disease is being treated because the doses used are low and the type of MAO inhibitor used (MAO type B inhibitors), particularly rasagiline, is less likely to have this effect.
Catechol O-methyltransferase (COMT) inhibitors (entacapone and tolcapone) slow the breakdown of levodopa and dopamine, prolonging their effects, and therefore appear to be a useful supplement to levodopa. These drugs are used only with levodopa. Tolcapone is seldom used because rarely, it damages the liver. However, tolcapone is stronger than entacapone and may be more useful if off effects are severe or long-lasting.
Some anticholinergic drugs (given for their anticholinergic effects) are effective in reducing the severity of a tremor and can be used in the early stages of Parkinson disease. Commonly used anticholinergic drugs include benztropine and trihexyphenidyl. Anticholinergic drugs are particularly useful for very young people whose most troublesome symptom is a tremor. These drugs are not used in older people because they have side effects (such as confusion, drowsiness, dry mouth, blurred vision, dizziness, constipation, difficulty urinating, and loss of bladder control) and because these drugs, when taken for a long time, increase the risk of mental decline. They may reduce tremor because they block the action of the neurotransmitter acetylcholine, and tremor is thought to be caused by an imbalance of acetylcholine (too much) and dopamine (too little).
Occasionally, other drugs with anticholinergic effects, including some antihistamines and tricyclic antidepressants, are used, sometimes to supplement levodopa. However, because these drugs are only mildly effective and because many anticholinergic effects are troublesome, these drugs are seldom used to treat Parkinson disease.
Amantadine,a drug sometimes used to treat influenza, may be used alone to treat mild Parkinson disease or as a supplement to levodopa. Amantadine probably has many effects that make it work. For example, it stimulates nerve cells to release dopamine. It is used most often to help control the involuntary movements that are side effects of levodopa.
Propranolol, a beta-blocker, may be used to reduce the severity of a tremor if the tremor is worsened by holding a limb in a position that requires resisting the pull of gravity (for example, holding the arms outstretched). Such tremors are called postural tremors.
Drugs Used to Treat Parkinson Disease
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. Magnetic resonance imaging (MRI) or computed tomography (CT) is used to locate the specific area to be stimulated. By stimulating this part, deep brain stimulation often greatly reduces involuntary movements and tremors and shortens the off part of the on-off effects.
In some countries, doctors remove or use a tiny electrical probe to destroy a small part of the brain that is severely affected. This procedure lessens symptoms. It may be followed by deep brain stimulation of a different part of the brain.
Psychotic and other mental symptoms, whether caused by Parkinson disease itself, a drug, or something else, are treated.
Using certain antipsychotic drugs—quetiapine, clozapine, or pimavanserin—to treat psychotic symptoms in older people who have Parkinson disease and dementia is not recommended. However, these drugs are still sometimes used because unlike other antipsychotics, they do not worsen the symptoms of Parkinson disease.
Antidepressants are used to treat depression. Antidepressants with anticholinergic effects (such as amitriptyline) are sometimes used. They may also help lessen the tremor. However, many other antidepressants are very effective and have fewer side effects. They include selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, paroxetine, selegiline, citalopram, and escitalopram, and other antidepressants, such as venlafaxine, mirtazapine, and bupropion.
Treatment of mental symptoms can help lessen problems with movement, improve quality of life, and sometimes delay the need to be put in an institution.
Because Parkinson 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 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 disease become severely disabled and immobile. They may be unable to eat, even with assistance. Dementia develops in about one third of them. Because swallowing becomes increasingly difficult, death due to aspiration pneumonia (a lung infection due to inhaling fluids from the mouth or stomach) 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.
Generic NameSelect Brand Names
trihexyphenidylNo US brand name
* This is the Consumer Version. *