An in-depth report on the causes, diagnosis, and treatment of Parkinson's disease.
What Is Parkinson’s Disease?
Parkinson’s disease is a neurological disorder that affects movement, muscle control, and balance. Parkinson’s disease most commonly affects people 55 - 75 years old, but it can also develop in younger people. The disease is usually progressive, with symptoms becoming more severe over time.
Symptoms of Parkinson’s Disease
Parkinson’s disease may be difficult to diagnose in its early stages. The disease is generally diagnosed on the basis of symptoms, which may include:
Tremors (shaking) in the hands, arms, legs, and face
Slowness of movement, especially when initiating motion
Difficulty with walking, balance, and coordination
Difficulty eating and swallowing
Depression and difficulties with memory and thought processes
There is no cure for Parkinson’s disease. Treatments focus on controlling symptoms and improving quality of life.
Lifestyle Changes. Good nutrition, regular exercise, and stress management can make living with Parkinson’s easier.
Rehabilitation Therapy. Physical therapy is an important part of Parkinson’s treatment. Speech and occupational therapy are also helpful. Rehabilitation can help improve balance, mobility, speech, and functional abilities.
Medications. Because Parkinson’s disease symptoms are due to a deficiency of the brain chemical dopamine, the main drug treatments help increase dopamine levels in the brain. Levadopa, usually combined with carbidopa, is the standard drug treatment. Other types of medication may also be used. Unfortunately, many of these drugs can cause side effects and lose effectiveness over time.
Surgery. In some cases of advanced-stage Parkinson’s disease, surgery may help to control motor problems. Deep brain stimulation is currently the preferred surgical method.
- Deep brain stimulation may be appropriate for patients with earlier stage Parkinson’s, according to a study in the New England Journal of Medicine. This surgical approach is currently recommended for select patients with advanced Parkinson’s.
- Low-intensity treadmill exercise –walking on a treadmill at a slow, comfortable speed-- helps improve gait speed as well as cardiovascular fitness, suggests a study in JAMA Neurology. Researchers found that stretching and resistance exercises were best for improving muscle strength.
- Physical therapy can help provide short-term benefits for patients with Parkinson’s, according to a report in the British Medical Journal. The researchers used a variety of techniques (hands-on exercises, treadmill training, dance, tai chi) to evaluate physical therapy’s effects on walking speed, mobility, balance, and falls.
Parkinson's disease (PD) is a slowly progressive neurological disorder that affects movement, muscle control, and balance. Parkinson’s disease is part of a group of conditions called motor system disorders, which are associated with the loss of dopamine-producing brain cells. These dopamine-associated motor disorders are referred to as parkinsonisms.
Parkinson's Disease and Dopamine Loss
Parkinson's disease occurs from the following process in the brain:
- PD develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra.
- Nerve cells in the substantia nigra send out fibers to the corpus stratia, gray and white bands of tissue located in both sides of the brain.
- There the cells release dopamine, an essential neurotransmitter (a chemical messenger in the brain). Loss of dopamine in the corpus stratia is the primary defect in Parkinson's disease.
Dopamine deficiency is the hallmark feature in PD. Dopamine is one of three major neurotransmitters known as catecholamines, which help the body respond to stress and prepare it for the fight-or-flight response.
Loss of dopamine impairs the nerves and muscles controlling movement and coordination, resulting in the major symptoms of Parkinson's disease. Dopamine also appears to be important for efficient information processing, and deficiencies may also be responsible for the problems in memory and concentration that occur in many patients.
The causes of Parkinson's disease are unknown. A combination of genetic and environmental factors likely plays a role.
Specific genetic factors appear to play a strong role in early-onset Parkinson's disease, an uncommon form of the disease. Multiple genetic factors may also be involved in some cases of late-onset Parkinson's disease.
Environmental factors are probably not a sole cause of Parkinson's disease, but they may trigger the condition in people who are genetically susceptible.
Some evidence implicates pesticides and herbicides as possible factors in some cases of Parkinson's disease. A higher incidence of parkinsonism has long been observed in people who live in rural areas, particularly those who drink private well water or are agricultural workers.
The average age of onset of Parkinson's disease is 55. About 10% of Parkinson's cases are in people younger than 40 years old. Older adults are at higher risk for both parkinsonism and Parkinson's disease.
Parkinson’s disease is more common in men than in women.
People with siblings or parents who developed Parkinson's at a younger age face an increased risk for the condition. However, relatives of patients who developed Parkinson’s at an older age appear to have an average risk.
Race and Ethnicity
African-Americans and Asian Americans appear to have a lower risk than Caucasians.
Possible Protective Factors
Both smoking and coffee drinking are associated with a lower risk for PD.
Smoking and Nicotine. Cigarette smokers appear to have a lower risk for Parkinson's disease, indicating possible protection by nicotine. This finding is, of course, no excuse to smoke. The few studies on nicotine replacement as a treatment for Parkinson’s have not provided any strong evidence that nicotine therapy provides benefits.
Coffee Consumption. Some studies suggest that the risk for PD in coffee drinkers is lower than for non-coffee drinkers. In a 30-year study of Japanese-American men, coffee consumption was associated with a lower risk for Parkinson's disease, and the more coffee they drank, the lower their risk became.
Parkinson's disease (PD) is not fatal, but it can reduce longevity. The disease progresses more quickly in older patients, and may lead to severe incapacity within 10 - 20 years. Older patients also tend to have muscle freezing and greater declines in mental function and daily functioning than younger people. If PD starts without signs of tremor, it is likely to be more severe than if tremor is present.
Parkinson's disease can seriously impair the quality of life in any age group. In addition to motor symptoms (motion difficulties, tremors), Parkinson’s can cause various non-motor problems that have significant physical and emotional impacts on patients and their families.
Swallowing problems (dysphagia) are sometimes associated with shorter survival time. Loss of muscle control in the throat not only impairs chewing and swallowing, which can lead to malnourishment, but also poses a risk for aspiration pneumonia. Swallowing problems can also interfere with adequate consumption of fiber and fluid, which can worsen constipation.
Emotional and Behavioral Problems
Depression is very common in patients with Parkinson's. The disease process itself causes changes in chemicals in the brain that affect mood and well-being. Anxiety is also very common and may present along with depression.
Some drug treatments, particularly dopamine agonists, can cause poor impulse control and compulsive behaviors, such as gambling, shopping, and increased sexuality. Patients who have pre-existing tendencies for novelty-seeking behavior, or a family or personal history of alcohol abuse, may be more likely to develop these problems. Deep brain stimulus (DBS) surgery may also increase the risk for compulsive gambling in patients who have a history of gambling.
Cognitive and Memory Problems
Impaired Thinking (Cognitive Impairment). Defects in thinking, language, and problem solving skills may occur early on or later in the course of the disease. These problems can arise from the disease process or from side effects of medications used to treat Parkinson’s. Patients with PD are slower in detecting associations, although (unlike in Alzheimer's disease) once they discover them they are able to apply this knowledge to other concepts.
Dementia. Dementia occurs in about two-thirds of patients with Parkinson’s, especially in those who developed Parkinson’s after age 60. Dementia is significant loss of cognitive functions such as memory, judgment, attention, and abstract thinking. It is most likely to occur in older patients who have had major depression. PD marked by muscle rigidity (akinesia), rather than tremor, and early hallucinations also increase the risk for dementia. (Visual hallucinations can also occur as a side effect of dopamine medication.) Unlike Alzheimer's, language is not usually affected in Parkinson's-related dementia.
Excessive daytime sleepiness, insomnia, and other sleep disorders are common in PD, both from the disease itself and the drugs that treat it. Bladder problems can also contribute to sleep disturbances. Many patients also suffer from nighttime leg cramps and restless legs syndrome. Some of the medications used for Parkinson's may cause vivid dreams as well as waking hallucinations.
Although Parkinson's disease and its treatments can cause compulsive sexual behavior, the disease can also cause a loss of sexual desire in both men and women. For men, erectile dysfunction can be a complication of Parkinson’s.
Bowel and Bladder Complications
Constipation is a common complication of Parkinson’s disease. It is often caused by muscle weakness that can slow down the action of the digestive system. Weakness in pelvic floor muscles can also make it difficult to defecate. In addition, swallowing problems associated with muscle weakness may make it difficult to eat enough fiber-rich foods and drink enough fluids, which can also cause constipation. Constipation may also occur as a side effect of some medications.
Patients with Parkinson’s disease frequently experience urinary incontinence, including increased urge and frequency. Parkinson’s can also cause urinary retention (incomplete emptying of the bladder).
Decreased Sense of Smell. Many patients experience an impaired sense of smell.
Vision Problems. Vision may be affected, including impaired color perception and contrast sensitivity.
Pain. Painful symptoms associated with Parkinson’s disease include muscle numbness, tingling, and aching. Pain in Parkinson’s is often a result of dystonia, involuntary muscle contractions and spasms that can cause twisting and jerking.
Patients with PD often develop skin problems, including excessively oily, dry, or flaking skin. Of greatest concern, Parkinson’s disease appears be associated with a higher risk for developing melanoma (an aggressive skin cancer). Patients with Parkinson's disease should have regular screenings with a dermatologist to check for skin changes that may indicate melanoma.
Parkinson's disease (PD) symptoms often start with tremor, which may occur in the following ways:
- Tremors may be only occasional at first, starting in one finger and spreading over time to involve the whole arm. The tremor is often rhythmic, 4 - 5 cycles per second, and frequently causes an action of the thumb and fingers known as pill rolling.
- Tremors can occur when the limb is at rest or when it is held up in a stiff unsupported position. They usually disappear briefly during movement and do not occur during sleep.
- Tremors can also eventually occur in the head, lips, tongue, and feet. Symptoms can occur on one or both sides of the body.
About a quarter of patients with Parkinson’s do not develop tremor.
Motion and Motor Impairment
Many PD symptoms involve motor impairment caused by problems in the brain nerves that regulate movement:
- Slowness of motion, particularly when initiating any movement (a condition called akinesia or bradykinesia), is one of the classic symptoms of Parkinson's disease.
- Patients may eventually develop a stooped posture and a slow, shuffling walk. The gait can be erratic and unsteady. After several years, muscles may freeze up or stall, usually when a patient is making a turn or passing through narrow spaces, such as a doorway. Patients' posture can be unstable, and they have an increased risk for falls.
- Intestinal motility (the ability to swallow, digest, and eliminate) may slow down, causing eating problems and constipation.
- Muscles may become rigid. This symptom often begins in the legs and neck. Muscle rigidity in the face can produce a mask-like, staring appearance.
- Motor abnormalities that limit action in the hand may develop in late stages. Handwriting, for instance, often becomes small.
- Normally spontaneous muscle movements, such as blinking, may need to be done consciously.
- Patients may develop speech problems, including soft voice or slurred speech.
Other Symptoms of Parkinson's Disease
Parkinson’s disease also causes non-motor symptoms, including sleep problems, gastrointestinal and urinary disorders, sexual dysfunction, decreased sense of smell, and depression and anxiety. [See Complications section of this report.]
Sialorrhea (drooling) is a common and bothersome symptom for those with Parkinson's disease. It can cause chapped skin and lips around the mouth, dehydration, an unpleasant odor, and social embarrassment.
Parkinson’s disease can be difficult to diagnose in its early stages. Doctors base their diagnosis on the patient’s medical history and symptoms evaluated during a neurological exam. No laboratory or imaging tests can diagnose Parkinson’s, although brain scans such as computed tomography (CT), magnetic resonance imaging (MRI), or positron-emission tomographic (PET) may be used to rule out other neurological disorders.
A medical and personal history should include any relevant symptoms as well as any medications taken, and information on other conditions the patient may have.
In a neurological exam, the doctor will ask the patient to sit, stand, walk, and extend their arms. The doctor will observe the patient’s balance and coordination. Parkinson's may be suspected in patients who have at least two of the following four symptoms, especially if they are more obvious on one side of the body:
Tremor (shaking) when the limb is at rest
Slowness of movement (bradykinesia)
Rigidity, stiffness, or increased resistance to movement in the limbs or torso
Poor balance (postural instability)
Drug Challenge Test
A levodopa challenge test may confirm a diagnosis of Parkinson's disease. If patients' symptoms improve when they take levodopa, they likely have Parkinson's, ruling out other neurological diseases.
Tests for Depression and Dementia
The American Academy of Neurology (AAN) recommends the Beck Depression Inventory or the Hamilton Depression Rating Scale to screen for depression in patients with Parkinson's disease. The AAN recommends the Mini Mental State Examination (MMSE) and Cambridge Cognitive Examination (CAMCOG) tests to screen for dementia. During these tests, the patient answers a series of questions.
Ruling out Conditions that Mimic Parkinson's Disease
Parkinsonism Plus Syndromes. Parkinson’s disease is the most common type of parkinsonism. Parkinsonism refers to a group of movement disorders that share similar symptoms with Parkinson’s disease, but also have unique symptoms of their own. About 15% of parkinsonism cases are due to conditions called Parkinson’s plus syndromes (PPS) or atypical parkinsonism. These syndromes include:
Corticobasal degeneration. Marked by apraxia (inability to perform coordinated movements or use familiar objects), stiffness that is more severe than typical Parkinson’s disease, and twitching or jerking in the hand.
Lewy body dementia. One of the most common types of progressive dementia. Symptoms include visual hallucinations and loss of spontaneous movement.
Multiple system atrophy. Symptoms include fainting, constipation, erectile dysfunction, urinary retention, and loss of muscle coordination.
Progressive supranuclear palsy. Marked by frequent falls, personality changes, and difficulty focusing the eyes.
Patients with PPS often have earlier and more severe dementia than those with Parkinson’s disease. In addition, they do not usually respond to medications that are used to treat Parkinson’s disease.
Other Neurologic Conditions. Many medical conditions may cause some symptoms of Parkinson's disease and parkinsonism. Hardening of the arteries (arteriosclerosis) in the brain can cause multiple small strokes, which can produce loss of motor control. Alzheimer’s disease can share similar symptoms with Parkinson’s and the conditions can exist together.
Medications. Several drugs, including antipsychotic and antiseizure medications, can cause Parkinson’s-type symptoms.
There is no cure for Parkinson’s disease, but drugs, physical therapy, lifestyle changes, and surgical interventions can help control symptoms and improve quality of life.
Treatment for Parkinson's Disease
Treatment for this complicated condition must be individualized. Patients must work closely with doctors and therapists throughout the course of the disease to tailor a treatment program to their particular and changing needs. No treatment method, including drug therapy, has been proven to change the course of the disease or slow disease progression. But many treatments can help ease symptoms and restore normal functioning for long periods of time.
The decision to start drug therapy usually arises when motor symptoms (movement problems, muscle rigidity, tremors) begin to interfere with daily functioning. The main types of drugs for treating Parkinson’s disease are:
- Dopamine agonists
- MAO-B inhibitors
All of these drugs have side effects. Your doctor will discuss with you the risks and benefits of various drugs, and will take into consideration such factors as your overall health, age, symptoms, stage of Parkinson’s, and other medical conditions you may have.
In general, levodopa/carbidopa is the standard drug for treating Parkinson’s throughout its disease course, but other drugs may be used for its earlier stages. When levodopa is used for many years, it can “wear off” and symptom improvement (“on" time) may decrease while symptom worsening (“off" time) increases. Motor symptoms may also fluctuate unpredictably. Your doctor may adjust the dosage or add another drug to your regimen to help boost levodopa’s effectiveness.
Treatment for Advanced Parkinson's
For patients with advanced Parkinson’s disease whose symptoms can no longer be controlled by medication, surgical treatment with deep brain stimulation may be an option. (Some recent research suggests this treatment may also be helpful for patients in earlier stages of the disease). Home modifications (wheelchair ramps, grab bars and handrails) can help improve functional abilities and independent living. Treatment goals for all stages of Parkinson’s disease should focus on providing patients with safety, comfort, and quality of life.
Treatments for Other Symptoms of Parkinson's
Conditions associated with non-motor impairment symptoms of Parkinson's disease may need a variety of treatments.
Depression. Medications for PD-associated depression include older drugs such as the tricyclic amitriptyline (Elavil) as well as newer antidepressants, including selective serotonin-reuptake inhibitors (SSRIs) and serotonin-norepeinephrine reuptake inhibtors (SNRIs) such as fluoxetine (Prozac, generic), sertraline (Zoloft, generic), paroxetine (Paxil, generic), and venlafaxine (Effexor, generic). Doctors need to monitor antidepressants to make sure they do not worsen motor symptoms. .
Psychotic Side Effects. Psychosis in Parkinson’s disease is often a side effect of medication. Doctors first try to adjust the dose of PD medications to see if psychotic side effects decrease without motor symptoms increasing. In some cases, a doctor may prescribe an antipsychotic drug, usually quetiapine (Seroquel). The antipsychotic clozapine (Clozaril, generic) is also considered appropriate for patients with Parkinson’s but it can have a serious side effect of lowering white blood cell count. Certain types of antipsychotic medications, such as olanzapine (Zyprexa) and risperidone (Risperdal), should not be used for patients with PD because they can worsen Parkinson’s symptoms.
Dementia. The cholinesterase inhibitor drugs donepezil (Aricept) and rivastigmine (Exelon) are used to treat Alzheimer’s disease and are sometimes used for Parkinson’s. (Rivagstigmine is FDA-approved for treatment of Parkinson’s dementia.) These drugs typically have only a very modest benefit on cognitive function. .
Daytime Sleepiness and Fatigue. Modafinil (Provigil), a drug used to treat narcolepsy may be helpful for patients with sleepiness related to their disease. Methylphenidate (Ritalin, generic) may be considered for patients who experience fatigue.
Erectile Dysfunction. PDE5 inhibitor drugs such as sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), and avanafil (Stendra) can be helpful for men with Parkinson's disease who suffer from erectile dysfunction. However, these drugs may worsen orthostatic hypotension (lightheadedness or dizziness that occurs when suddenly standing up), a side effect of some PD medications.
Constipation. Dietary changes should be the first step for addressing constipation. It is important to increase overall fiber and fluid consumption, but this can be difficult for patients who have swallowing problems. Taking a stool softener such as docusate (Colace, generic) on a daily basis may help with bowel movements. For laxatives, bulk-forming fiber laxatives are considered the safest and are not habit-forming. They include psyllium (Metamucil, other brands, generic) and wheat dextrin (Benefiber, generic). Stimulant laxatives should be avoided as they can worsen bowel problems if used on a long-term basis. Check with your doctor for advice about using other types of laxatives, suppositories, and enemas. Regular exercise is also helpful for constipation.
Drooling. Glycopyrrolate, scopolamine, and injections of botulinum toxin may be used to relieve drooling symptoms.
Levodopa, also called L-dopa, which is converted to dopamine in the brain, remains the gold standard for treating Parkinson's disease symptoms. The standard preparations (Sinemet, Parcopa) combine levodopa with carbidopa, which improves the action of levodopa and reduces some of its side effects, particularly nausea. Sinemet is swallowed as a pill. Parcopa is a tablet that dissolves under the tongue.
Dosages vary, although the preparation is usually taken in three or four divided doses per day. This medication works best on an empty stomach, but some patients find this causes nausea and prefer to take it with a light meal or snack. If taking levodopa/carbidopa along with food, it is important to avoid high-protein foods as they can interfere with drug absorption.
Levopdopa/carbidopa helps improve mobility for many patients. It works best for treating difficulties with movement (akinesia) and muscle stiffness. It may be less effective for treating tremor, balance, coordination, and posture.
Levodopa/carbidopa does not prevent Parkinson’s disease progression. Over time, the dose of the drug has to be increased to be effective.
Side Effects. Many side effects of levodopa/carbidopa can be minimized by adjusting dosage. The most common side effects include nausea, vomiting, loss of appetite, low blood pressure, dizziness, and confusion.
Serious side effects include:
- Dyskinesia refers to unvoluntary muscle movements. Dyskinesia can take many forms, most often uncontrolled flailing of the arms and legs or chorea, rapid and repetitive motions that can affect the limbs, face, tongue, mouth, and neck. Dyskinesia may develop after long-term use of levodopa.
- Serious psychiatric side effects include agitation, hallucinations, delusions, and psychosis.
“Wearing-Off” Effect and “On-Off” Time. After several years of taking levodopa, many patients find that the drug’s helpful effects last for shorter periods of time and that symptoms return before the next dose is due to be taken. When the medication “wears off” in between doses, patients may find their symptoms suddenly worsen (“off-time”). At other times of the day, symptoms may be well- controlled (“on-time”). Wearing off can develop gradually during the day, or it can occur intermittently and unpredictably.
An increase in dyskinesia (involuntary movements) and other motor symptoms (muscle stiffness, rigidity, slowness, cramping) are most commonly associated with the wearing-off effect. Some patients may also experience non-motor symptoms such as difficulty concentrating, anxiety, insomnia, fatigue, sweating, and trouble breathing. If symptoms improve when the next dose of levodopa/carbidopa is taken, this is a clear sign of the wearing-off effect.
There are different approaches for managing wearing off and off-time. Your doctor may recommend:
- Using a controlled-release formula of levodopa/carbidopa (Sinemet CR), which slowly releases the drug into your bloodstream throughout the day
- Switching to Stalevo, a levodopa/carbidopa drug that also includes COMT inhibitor entacaopone
- Adding another drug such as a COMT inhibitor, MAO-B inhibitor, or dopamine agonist to your current medication regimen.
Making some adjustments to your food schedule may also help with wearing off. Try to take levodopa/carbidopa on an empty stomach, at least 30 minutes before eating. High-protein foods can especially interfere with levodopa absorption.
Levodopa is converted into dopamine in the brain. In contrast, dopamine agonists mimic the action of dopamine by stimulating dopamine receptors in the brain. A dopamine agonist drug may be used as an initial medication in the early stages of PD to delay the need for levodopa, or it may be used along with levodopa/carbidopa in later stages of the disease. .
When used alone, these drugs are less likely to cause dyskinesia than levodopa, but they may be less effective than levodopa for controlling motor symptoms. There is debate about the value of dopamine agonists as first-line therapy for Parkinson’s disease. Some research suggests that early treatment with dopamine agonists may not provide any long-term advantages compared with starting treatment with levodopa/carbidopa.
Brands. Pramipexole (Mirapex, generic) and ropinirole (Requip, generic) are the most commonly prescribed oral dopamine agonists. Rotigotine (Neupro) is a skin patch that is applied once a day. Apomorphine (Apokyn) is a self-injectable dopamine agonist that is used as a rescue medication for quickly treating “off time” motor symptoms in advanced PD.
Side Effects. Common side effects of dopamine agonists include nausea, confusion, and leg swelling. More serious concerns include:
- Orthostatic hypotension (sudden drop in blood pressure upon standing up)
- Nightmares, hallucinations, and psychosis especially for patient with advanced disease
- Excessive sleepiness and sudden “sleep attacks”. Patients should be aware of this side effect, particularly if they drive.
- Compulsive behaviors. These are associated with a loss of impulse control and include compulsive gambling, sexual behavior, shopping, and eating.
- Heart failure may be a possible concern. In 2012, the FDA announced it was reviewing whether pramipexole may increase the risk for heart failure.
Monoamine Oxidase B (MAO-B) Inhibitors
MAO-B inhibitor drugs block monoamine oxidase B (MAO-B), an enzyme that inactivates dopamine. Selegiline (Eldepryl, Zelapar) and rasagiline (Azilect) are MAO-B inhibitors used for treating Parkinson’s disease. These drugs may be used alone in the early stages of PD to treat mild symptoms (such a tremor) and delay the need for levodopa. They may also be used in combination with levodopa in later stages to enhance the effects of levodopa and help manage motor fluctuations. Many patients notice only small benefits.
Side Effects. Common side effects of MAO-B inhibitors include flu symptoms, dizziness, and insomnia. More serious side effects may include agitation, confusion, and hallucination.
Talk with your doctor about any other medications (both prescription and over-the-counter) and supplements you are taking. MAO-B inhibitors can interact with a number of medications including narcotics, pain relievers, cough suppressants, and antidepressants (including the herbal remedy St. John’s wort). Foods high in the amino acid tyramine may cause a dangerous increase in blood pressure, particularly if you are taking a high dose of this medicine. Foods to be avoided include processed lunch meats, soy sauce, aged cheeses, and beer.
Catechol-O-Methyl Transferase (COMT) Inhibitors
Catechol-O-methyl transferase (COMT) inhibitor drugs are used along with levodopa/carbidopa to increase and prolong levodopa’s effectiveness and prevent “wearing off.” Entacapone (Comtan, generic) is the standard COMT inhibitor. Stalevo (generic) is a pill that combines entacapone, levodopa, and carbidopa.) A third COMT inhibitor, tolcapone (Tasmar), is only rarely prescribed due to its risks for liver damage.
Side Effects. COMT inhibitors are always used in combination with levodopa/carbidopa and may increase levodopa’s dyskinesia side effects. Other side effects may include low blood pressure when standing up (orthostatic hypotension), nausea, dizziness, diarrhea, and urine discoloration.
Since 2010, the FDA has been reviewing whether Stalevo may increase the risk for heart attack and stroke. The FDA is also reviewing whether Stalevo may increase the risk of prostate cancer.
Anticholinergics were the first drugs used for PD, but they have largely been replaced by dopamine drugs. They are generally used only to control tremor in the early stages. Among the many anticholinergics are trihexyphenidyl (Artane, Trihexane, generic) and benztropine (Cogentin, generic.
Side Effects. Anticholinergics commonly cause dryness of the mouth (which can actually be an advantage in some people who experience drooling). Other side effects are nausea, urinary retention, blurred vision, and constipation. These drugs can increase heart rate and worsen constipation. Anticholinergics can sometimes cause significant mental problems, including memory loss, confusion, and even hallucinations. People with glaucoma should use these drugs with caution.
Amantadine (generic) stimulates the release of dopamine and may be used to provide temporary relief of early mild symptoms such a tremor and rigidity. It is sometimes prescribed along with levodopa/carbidopa for advanced PD to help control motor fluctuations and dyskinesia.
Side Effects. Side effects are similar to those of anticholinergic drugs and may include swollen ankles and, in rare cases, mottled skin. Amantadine can also cause visual hallucinations, confusion, and memory loss.
Surgical procedures are recommended for specific patients with advanced Parkinson’s disease whose symptoms are not controlled by drug treatments. Surgical treatment cannot cure Parkinson's disease, but it may help control symptoms such as motor fluctuations and dyskinesia.
Deep brain stimulation is the current standard surgical approach for Parkinson’s disease. It has largely replaced pallidotomy and thalamotomy, older operations that destroy tissue in certain parts of the brain.
Deep Brain Stimulation
In deep brain stimulation (DBS), also called neurostimulation, an electric pulse generator controls symptoms such as severe tremors, wearing-off fluctuations, and dyskinesia. The generator is similar to a heart pacemaker. It sends electrical pulses to specific regions of the brain. Candidates most likely to benefit from DBS are those who have advanced Parkinson’s, have responded well to levodopa drug treatment, are younger age, and do not have significant cognitive or psychiatric problems. Some recent research suggests that DBS may also benefit patients in earlier stages of the disease who have early signs of motor symptoms.
For treatment of motor symptoms, DBS usually targets one of two areas of the brain: the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi). Research indicates that both areas equally likely to respond well to DBS. DBS targeting the STN may allow patients to use less medication, but treatment of this brain area may worsen depression, apathy, impulsivity, ease of using words, and falls.
For treatment of disabling tremors, DBS may be used to target the STN, GPi, or the ventral intermediate nucleus of the thalamus.
DBS should be performed by an experienced neurosurgeon who is trained in stereotactic neurosurgery (surgery that uses three-dimensional imaging to help target specific areas of the brain).
The procedure is performed as follows:
Before the procedure, the neurosurgeon uses magnetic resonance imaging (MRI), computed tomography (CT), or other types of imaging techniques to pinpoint the exact areas of the brain where the DBS electrodes will be inserted.
The neurosurgeon implants a tiny pulse generator near the collarbone, which is connected to four electrodes that have been implanted in the target area in the brain.
The generator delivers programmed pulses to this area, which the patient can turn on and off using a magnet held over the skin. When on, the pulses suppress symptoms.
The most common complication is infection at the surgical site.
The benefits of DBS appear to be long lasting, but it may take 3 - 6 months to achieve results. During this time, doctors may need to adjust the implanted device. Researchers are still trying to determine the best surgical techniques for implanting the DBS device, and how to best select the patients who are most likely to benefit.
Pallidotomy and Thalamotomy
Pallidotomy and thalamotomy are surgical procedures that destroy brain tissue in regions of the brain associated with Parkinson’s symptoms, such as dyskinesia, rigidity, and tremor. In these procedures, a surgeon drills a small hole in the patient’s skull and inserts an electrode to destroy brain tissue. Pallidotomy targets the global pallidus area. Thalamotomy targets the thalamus. Because these procedures permanently eliminate brain tissue, most doctors now recommend deep brain stimulation instead of pallidotomy or thalamotomy.
Surgical complications may include behavioral or personality changes, trouble speaking and swallowing, facial paralysis, and vision problems. Weight gain after surgery is also common.
Stem Cell Implantation
Scientists are investigating whether stem cells may eventually help treat Parkinson disease. Experimental surgery has shown promise using fetal brain cells rich in dopamine implanted in the substantia nigra area of the brain. Because the use of embryonic stem cells is controversial, researchers are studying alternative types of cells, including stem cells from adult brains and cells from human placentas or umbilical cords. All of this research is still preliminary.
No special diets or foods can slow the progression of Parkinson's disease, but certain dietary strategies may help with managing symptoms.
Protein. High levels of proteins can affect how much levodopa can reach the brain and can, therefore, reduce the drug's effectiveness. Avoiding protein altogether is not the solution, since malnutrition can result. Most doctors recommend reducing protein or eating most of your protein at the evening meal. Patients should discuss a low-protein diet and other nutritional strategies with their health team.
Good control of protein intake may help minimize fluctuations and wearing-off and may allow some patients to reduce their daily levodopa dosage.
Fruits, Vegetables, and Fiber. Eating whole grains, fresh fruits, and vegetables is the best approach for any healthy life. A diet rich in fruits and vegetables may help protect nerve cell function. Many of these foods are also often rich in fiber, which is particularly important for helping to prevent constipation.
If you are used to eating a low-fiber diet, you should try to gradually increase the amount of fiber. It is best to obtain dietary fiber, soluble or insoluble, in the natural form of whole grains, nuts, legumes, fruits, and vegetables. If it proves difficult to do so, psyllium, (found in products such as Metamucil), is an excellent soluble fiber supplement. Drinking lots of fluids is particularly important in preventing constipation.
Weight Loss. For reasons that are not completely understood, many patients with Parkinson’s disease experience weight loss. Parkinson’s disease can affect a person’s sense of smell and taste, which may make food lessappetizing. Tremors (shaking) and swallowing problems can make it more difficult and tiring to eat. If you find that you are losing weight without trying, talk with your doctor or a dietician about developing a diet plan that will meet your caloric needs.
Herbs and Supplements. There is currently no evidence for the effectiveness of any herb or dietary supplement in the treatment of Parkinson’s disease. Coenzyme Q10 is the most-studied supplement for PD. A high-quality study was unable to demonstrate benefits for patients with early-stage PD, although more research is being conducted.
Ginger is one natural remedy that has well-established properties for easing nausea. A simple tea made from boiling ginger root may help alleviate nausea symptoms associated with many Parkinson’s disease medications.
Be sure to let your doctor know about any herb or dietary supplement you are taking, or considering taking. Some products, such as St. John’s wort, can interact and interfere with the effectiveness of medications.
Regular exercise is important for patients in all stages of Parkinson’s disease. Exercise has a wide range of benefits. It can improve muscle strength and agility, which helps promote better walking and balance. Exercise can also help with controlling symptoms such as fatigue, constipation, and depression.
Types of Exercise. Doctors recommend that patients incorporate stretching, resistance, and aerobic exercise into their routine. Some suggestions include:
- In the gym, walking on a treadmill, even at low intensity, can help improve walking gait and speed as well as cardiovascular fitness. Cycling on a stationary bike is also good aerobic exercise.
- Stretching and resistance exercise is the best way to build muscle strength. Weight training is a type of resistance exercise.
- Tai chi, a Chinese martial art that emphasizes slow flowing motions and gentle movements, may help patients with mild-to-moderate Parkinson’s improve strength and balance and reduce the risk of falls. Yoga is also an excellent and gentle exercise for stretching, strengthening, and relaxation.
- Music helps patients move more smoothly and easily. Dance is an excellent way to increase flexibility and endurance.
For patients with more advanced Parkinson’s, certain exercise techniques can help with managing rigidity and gait issues. Patients should continually make efforts to practice movement, even simple ones, such as marching in place, making circular arm movements, and raising the legs up and down while sitting.
Reducing Muscle Freezing. Try to practice regular daily activities that simplify actions and reduce the incidence of muscle freezing. Most often, freezing occurs when a patient begins to move or is presented with an obstacle. The following tips may be helpful:
- Rock from side to side.
- If the legs feel frozen, lift the toes. This simple action may free spasm in some cases.
- Hum marching tunes. In fact, music helps patients to move and even to get out of bed in the morning.
- Divide actions into separate components, which may prevent freezing that occurs from trying to coordinate too many physical operations at one time. For instance, when going through a doorway, approach the door, stop at the door, open it, stop, and then walk through the doorway.
- Simply being touched by another person can sometimes release muscle freezing (although a patient with PD should never be pulled or pushed).
Gait Training. Practicing new methods for standing, walking, and turning may help retain balance and reduce the risk of falls. The following tips may be helpful:
- Take large steps when walking forward, raising the toes at the forward step, and hitting the ground with the heel.
- Take small steps while turning.
- When walking or turning, have the legs 12 - 15 inches apart to provide a wide base.
- Do not wear rubber or crepe-soled shoes because they grip the floor and may cause you to fall forward.
- Using devices that keep a rhythmic beat, such a metronome (a simple device used by musicians to keep time), may help to walk faster and take longer steps.
Patients with Parkinson’s can benefit from working with rehabilitative therapists. They include physical therapy, occupational therapy, and speech therapy. Patients may also find arts therapy (including dance therapy and music therapy) to be helpful.
Physical Therapy. Exercise is an important component of rehabilitation. Physical therapy can help with physical function and quality of life. It usually includes active and passive exercise, gait training, and practice in normal activities. A physical therapist can help with passive exercise, to stretch and manipulate muscles to help prevent deterioration and shortening. Active exercises are used to help range-of-motion, coordination, and speed. A physical therapist can also advise on how to best use mobility aids (such as canes, crutches, and scooters) and other assistive devices.
Speech Therapy. Speech therapy may help those who develop a monotone voice and lose volume. Certain techniques, such as the Lee Silverman Voice Technique, are designed specifically to help patients with Parkinson’s disease speak louder. A speech therapist can also help evaluate and monitor swallowing issues.
Occupational Therapy. Occupational therapists help patients learn how to improve their functioning and independence within their home and workplace environments. They can help patients better manage activities of daily living including bathing, dressing, and grooming. Occupational therapists can provide professional advice on what sort of adaptive tools, such as grab bars, should be used in the bathroom, bedroom, and kitchen. They can advise on mobility devices such as wheelchairs and scooters.
Relaxation techniques and staying mentally active are important for managing stress and dealing with feelings of depression and anxiety:
- Stress management techniques include deep breathing and other relaxation modalities, meditation, biofeedback, music therapy, yoga, tai chi, and massage therapy. Exercise is also an excellent way to reduce stress and can be incorporated into activities such as gardening and golf.
- Find new hobbies. Patients may find that symptoms interfere with activies they once enjoyed. Developing new hobbies can help you stay positive and keep you mentally alert.
- Caregivers need to evaluate and manage their own stress and fatigue levels. There are many support organizations and resources available to help caregivers deal with the challenges of caring for a loved one with Parkinson’s. Psychological counseling is also appropriate.
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Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.