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What is Parkinson's Disease?

More than one million people in the United States are doing battle with the neurodegenerative ravages of Parkinson's disease. This disease, which typically hits people past the age of 65, gradually strips away motor abilities, leaving them with a slow and awkward gait, rigid limbs, tremor, shuffling and a lack of balance. Patients can lose facial expression and sometimes the ability to speak. In as many as half, the disease also comes with psychiatric complications of anxiety and depression.

No one knows what causes Parkinson's. Most cases arise spontaneously; some are hereditary. What is known is that brain cells in the area of the brain called the "substantia nigra" die off. These are the cells which manufacture the molecule dopamine, a chemical that helps control muscle movement. Drug therapies have focused on replacing the dwindling supply of dopamine or addressing specific symptoms associated with the disease. Thanks to recent advances in the lab, including the pinpointing of several Parkinson's genes, research is exploding. Scientists are now picking apart newly discovered biochemical pathways involved in the disease and uncovering new targets for therapy, including neuromodulation.

What causes Parkinson’s disease (PD)?

Parkinson's disease is a progressive neurological disease involving loss of neurons in a part of the brain called the substantia nigra. This results in a reduction in the amount of the chemical dopamine, a chemical messenger or neurotransmitter. When 80 percent of dopamine in the brain is depleted, the symptoms of Parkinson's disease develop. The main symptoms are tremor, slowness of movement, stiffness and impairment of balance. It is a highly treatable disease and the life span is not shortened.

The loss of dopamine in an area of the brain called the striatum is the main chemical abnormality and there is a correlation between dopamine loss in this area of the brain and the severity of the symptoms. It is thought that exposure to some unidentified environmental toxin in a person who has a certain genetic predisposition causes the person to develop the disease. Inside the dopamine neurons, there are structures called mitochondria which use oxygen to turn food into energy. These mitochondria may be damaged in people with Parkinson's disease.

Who gets Parkinson's?

Parkinson's Disease affects less than one percent of the general population, but three percent or more of those are older than 60. There are approximately 60,000 people diagnosed with the disease per year. The average age of onset of symptoms is 60, but five to ten percent of patients have symptoms before the age of 40. The prevalence is expected to triple in the next 50 years.

How is Parkinson's diagnosed?

Persons are diagnosed based on the symptoms they have and the physical examination. There are no standard laboratory tests available although testing is often done to exclude other similar diseases. A significant improvement in symptoms related to taking the medication carbidopa/levodopa is helpful in making the diagnosis since all patients with Parkinson's Disease respond to this medication.

What are the primary symptoms of Parkinson's?

Typically, as the disease progresses, persons with Parkinson's disease will also suffer from impairment of the autonomic nervous system, develop difficulty with sleep and speech, and sustain physical injuries due to falls. Frequently, psychiatric problems will develop as well, particularly depression and cognitive impairment.

The following are the most common symptoms of Parkinson's disease. However, each individual may experience symptoms differently. Symptoms may include:

  • muscle rigidity – stiffness when the arm, leg, or neck is moved back and forth.
  • resting tremor – tremor (involuntary movement from contracting muscles) that is most prominent at rest.
  • bradykinesia – slowness in initiating movement.
  • postural instability – poor posture and balance that may cause falls; gait or balance problems.

Muscle Rigidity:
Rigidity is felt as a stiffness or tightness in the arms, legs, neck or trunk. It is not uncommon for a patient to be evaluated and treated for arthritis in a shoulder prior to diagnosis of Parkinson's disease. This symptom responds well to anti-Parkinson's medications.

Resting Tremors:
The tremor in Parkinson's disease is a characteristic one in that it occurs at rest rather than when the limb is being used and it is fairly slow occurring at a rate of about five times per second. It usually begins in one arm, but spreads to involve the other side, sometimes the legs and occasionally the jaw. The tremor is usually reduced or eliminated when the limb is being used in some purposeful way. For this reason, the tremor is often not functionally limiting. This symptom responds fairly well to anti-Parkinson's medications. For some patients, however, medications are not effective in treating the tremors. In these individuals, deep brain stimulators implanted in the thalamus can achieve very satisfactory results.

Bradykinesia (Slowness of Movement):
Slowness of movement may be very disabling and is one of the major symptoms for which treatment is sought. It may impair ability to perform tasks involving the arms such as writing and buttoning, and the legs as when walking. The handwriting is characteristically small (micrographia) and this may be one of the first signs noted by some patients. This symptom responds well to anti-Parkinson's medications.

Postural Instability (Walking and Balance Difficulties):
One of the first signs of Parkinson's disease is often a decrease in the natural swing of one of the arms when walking. As the disease progresses, this involves both sides and there may be a difficulty in taking large steps so that a shuffling gait develops. There may be a tendency to take rapid short steps and to even have trouble stopping. With advancing disease, there may be "freezing" episodes where the feet feel as if they are glued to the floor and taking any steps at all becomes very difficult. Also with advancing disease, there may be impairment of balance. This may be related to a diminished ability to make corrective adjustments in the posture to prevent falling. When these later symptoms develop, physical therapy and the use of assistive devices such as canes and walkers, is recommended. Unfortunately, the balance problems do not respond well to anti-Parkinson's medications.

Other symptoms of Parkinson's Disease:

Symptoms of Parkinson's disease vary from patient to patient. The symptoms may appear slowly and in no particular order. Early symptoms may be subtle and may progress over many years before reaching a point where they interfere with normal daily activities.

Autonomic Impairment

The autonomic nervous system controls many of the automatic body functions such as control of heart rate, blood pressure, sweating and digestion. The autonomic system is often involved in Parkinson's disease as follows:

Constipation is a common complaint in many people and increases with age. Persons with Parkinson's disease are often more troubled with it because the transit of food through the gastrointestinal (GI) tract is slowed. Relative inactivity also slows down the GI tract. Natural methods, such as ensuring regular activity, drinking plenty of fluids and eating more fiber can be helpful. Stool softeners, such as Colace can be used and if needed laxatives. Failure of attending to the problem can lead to severe constipation with the possibility of developing obstructions.

Urinary Problems:
Some patients can have difficulty with urination and this may include an urgency to urinate where there is little warning of the need to urinate. Because mobility may be impaired in these patients they may not be able to make it to the bathroom in time and incontinence may develop. There can also be the problem of inability to fully empty the bladder. If incontinence is present, protective garments are often helpful. Depending upon the problem, medications can also be helpful.

Orthostatic Hypotension:
Both the disease process and the medications used to treat it can cause the blood pressure to fall when a person with Parkinson's disease stands up. This can result in a feeling of lightheadedness and faintness and can sometimes lead to the person actually passing out and falling. Especially in the morning after the patient has been laying flat for several hours, it is important to get up slowly, perhaps sitting at the bed for a few minutes before arising. Because fluid can settle in the veins in the legs, the use of support stockings can sometimes be helpful. There are also several medications to treat this problem including Florinef (fludrocortisone), Midodrine (ProAmatine), and Yohimbine. Persons who have had hypertension are often able to come off medications previously being used to control hypertension, but this should be done according to a physician's orders.

Sexual Dysfunction:
Sex can be more difficult in part because individuals with Parkinson's disease have difficulty with mobility. The tremors in Parkinson's disease are often greatly increased with excitation and this can be an interference. Some men can have difficulty in achieving and maintaining an erection. The medication "Viagra" can be helpful in many of these cases.

Rarely, some patients with Parkinson's (both men and women) can develop an abnormal increase in their sexual drive and behaviors that causes problems in their life or with others. When this happens, it can be related to anti-parkinsonian medication and should be brought to the attention of ones doctor.

Excessive Salivation:
Rather than an over production of saliva, excessive salivation (or drooling) is likely the result of an accumulation of saliva in the mouth due to less frequent swallowing. Feedback therapies along with speech therapy to encourage more frequent swallowing of the saliva is often helpful. If the drooling becomes severe, drops of ophthalmic solutions of atropine under the tongue are helpful.

Motor Complications

As the disease advances, the response to medications used to treat the Parkinson's disease can become less reliable.

Wearing off of Medications:
The first motor complication to develop is usually that the levodopa or dopamine agonist does not effectively treat the symptoms through to the next scheduled dose. This can usually be helped by decreasing the time between doses, adding a dopamine agonist to the medical regimen of persons on levodopa, or adding Comtan (which extends the effectiveness of levodopa).

Dyskinesias are involuntary, irregular, twisting or writhing movements occurring when a dose of levodopa is at its highest levels in the brain of individuals with relatively advanced Parkinson's disease.

Dyskinesias begin to occur in 50 percent of patients approximately five years after they begin levodopa, but in an even higher percentage of patients who begin treatment at a young age. Dyskinesias can often be alleviated by reducing the dose of medication of Sinemet or the dopamine agonist. Amantadine is a medication that has been used to treat the symptoms of Parkinson's disease for many years. More recently it has been shown to have a modest effect in reducing dyskinesias. If the dyskinesias are incapacitating and cannot be treated by adjustments in medications, Deep Brain Stimulation (DBS) is an alternative.

Drug Failure:
Occasionally, a dose of medication may seem to fail to have any effect on the symptoms of Parkinson's disease. This may be due to insufficient absorption of the medication. High protein meals can compete with the levodopa getting into the brain. Under these circumstances some patients can overcome the problem by delaying major protein consumption to the evening hours. For isolated "failed" doses, an extra dose can be taken and chewing a portion of the levodopa tablet can enable quicker absorption and action of the drug.

Psychiatric Symptoms

Depression is a very common symptom in people with Parkinson's Disease occurring in approximately 40 to 50 percent of people. It can often be the first symptom appearing, even before any changes in movement develop. This suggests that depressive disturbances are related to the underlying brain disease that also causes changes in motor function. However, depression can also reflect an emotional reaction to the disease symptoms.

Because the motor symptoms may limit work and recreational activities the person was previously able to do, a loss is experienced along with some changes in life style. Strong social supports are helpful and counseling by social workers or psychologists is often helpful. Antidepressant medications are effective as well and should be used when appropriate.

Cognitive Impairment:
Cognitive impairment to some degree occurs in most patients as Parkinson's disease advances. The changes may be subtle and have no effects on daily functioning. Others have more significant problems with memory, attention, or planning. In patients with advanced disease, about 25 percent of Parkinson's patients develop a dementia syndrome. It may also be caused by other treatable conditions such as hypothyroidism and vitamin B12 deficiency. These other causes should be fully investigated.

In addition, many medications used to treat Parkinson's disease can cause or worsen cognitive impairment. This is particularly true about the anticholinergic medications (e.g., Artane) and the dopamine agonists. Of the medications used to treat Parkinson's disease, levodopa is the least likely to cause cognitive problems.

During the course of their illness, it is estimated that 40-to-50 percent of patients with Parkinson's disease will experience psychotic symptoms, including hallucinations and/or delusions. Hallucinations are abnormal sensory experiences in which the individual sees, hears, smells, feels, or tastes something that is not actually present in the environment. In PD, visual hallucinations are most common. They may involve seeing people or animals or distortions of what is actually there, such as perceiving that a stick is a snake until there is closer inspection of the object. Delusions are fixed, false beliefs that a person maintains even despite evidence to the contrary. These may include paranoid thoughts, including delusional jealousy that their spouse is having another relationship. In PD, psychotic symptoms are most commonly a side effect of antiparkinsonian medications, although factors such as dementia or mood disorders increase the risk for psychosis.

Medical illnesses or medications can also cause a delirium or confusional state that involves psychosis. In many cases of visual hallucinations, insight is retained and some patients may even find the experience amusing. Some patients are reluctant to reveal they have these symptoms because of embarrassment or fears of being thought of "as crazy". It is important, however, that patients report psychotic symptoms to their doctor, since they can often be treated by adjusting antiparkinsonian medications or by adding an antipsychotic medicine when the psychosis becomes more disruptive.

Hallucinations and delusions usually occur in persons with advanced disease who are on multiple medications. The medications used to treat Parkinson's disease that are most likely to cause these symptoms are the anticholinergic medications (Artane, Cogentin), Eldepryl (Selegiline), and the dopamine agonists such as Permax (Pergolide), Pramapexole (Mirapex), and Ropinirole (Requip). If a reduction in medications is not possible or is ineffective in stopping the hallucinations or delusions, there are other medications available to treat them.

Anxiety is a common problem in Parkinson's disease that is often overlooked as a management issue. Sometimes, anxiety is an understandable psychological response to motor impairments or other personal concerns. However, 25 to 40% of patients have clinically significant anxiety disorders. These can involve problems with generalized and nonspecific anxiety, phobias of going out in public or being in crowded or closed spaces, or panic disorder, which was seen in 25 percent of patients in some series.

The development of anxiety disorders appears related to the underlying neurodegenerative processes associated with Parkinson's disease, especially since many individuals have new onset anxiety disorders early in their course of PD and sometimes even before the motor symptoms of Parkinson's disease are evident. It is important that patients inform their doctor about anxiety symptoms since they can be very disabling if untreated. Some patients can control symptoms with behavioral techniques and others require medications. Many antidepressant medications treat anxiety disorders very effectively.

Other anti-anxiety, sleep-inducing, or anti-psychotic medications may also be needed. Anxiety symptoms occur as a frequent feature of depressive disorders, which would be the primary focus of treatment. It is also important to distinguish whether anxiety symptoms are related to fluctuations in antiparkinsonian medication effects. These are termed non-motor fluctuations and warrant adjustments in the antiparkinsonian medication, although other anxiety treatments may also be needed.

Other Behavioral Disturbances:
Rarely, Parkinson's disease patients will develop problem behaviors such as gambling, hypersexuality, or other impulse control problems. It is often a great surprise to the patient and their family that such symptoms can occur in Parkinson's disease, and without such knowledge, many patients will try to conceal such problems. Importantly, such symptoms can be treated and often relieved with adjustments in antiparkinsonian medications or the addition of antipsychotic medications.

Sleep Symptoms

Sleep problems are present in most patients with Parkinson's Disease.

  1. Difficulty falling asleep. In persons with severe tremors, there may be an exacerbation of the tremors when laying down in bed resulting in problems falling asleep. Anxiety disorders and depression may cause a delay in falling asleep as it does in persons without Parkinson's Disease. These should be treated with antianxiety or antidepressant medications. Avoidance of beverages containing caffeine, regular afternoon exercise, and avoiding watching television or reading in bed are recommended.

  2. Difficulty staying asleep. There are often problems in staying asleep in part because involuntary movements during sleep awaken the patient. Periodic movements of sleep may be effectively treated with a bed time dose of levodopa or a dopamine agonist. Early morning awakening can be a sign of depression and this should be considered. Sedating antidepressants are often helpful.

Daytime Sleepiness:
Excessive sleepiness during the daytime can result from poor sleep but can also be a side effect of the medications used to treat Parkinson's disease. It is important to distinguish between these two possibilities. If sleep quality is not the problem and adjustments in medications do not improve the sleepiness, the medication Provigil may be helpful, although it is not approved by the FDA for use in Parkinson's disease.

Restless Leg Syndrome:
It is estimated that about eight percent of the U.S. population may have this neurologic condition. The incidence increases in individuals with Parkinson's Disease. Individuals with this disorder describe bothersome sensations deep within the legs such as itching, pulling, tugging, or creepy-crawly sensations. The person has a strong urge to move the legs or occasionally the arms. Symptoms are worse at night and when at rest. In Parkinson's patients, symptoms may be worse during "off" times.

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