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Parkinson’s Disease (PD) is a degenerative, progressive neurologic disorder that affects nerve cells in deep parts of the brain that are responsible for relaying messages that plan and control body movement. When these nerve cells die, PD symptoms such as tremor, slowness of movement, stiffness, and balance problems begin to occur. The cause of PD is largely unknown, and the disease cannot be cured or slowed at this time. Treatment focuses on reducing symptoms to enable a normal, active lifestyle. To understand Parkinson's, it is helpful to understand how the nervous system works and how PD affects normal functions (see Anatomy of the Brain). Nerve cells, or neurons, are the basic building blocks of the nervous system. The neuron is responsible for sending and receiving nerve impulses or messages. Try to picture electrical wiring in your home. An electrical circuit is made up of numerous wires connected in such a way that when a light switch is turned on, a light bulb will beam. Similarly, a neuron that is excited will transmit its energy to neurons that are next to it. Neurons have a central cell body attached to slender, branching "arms." There are two types of arms: dendrites are like antennae and carry messages, or impulses, to the cell body, while axons carry messages away from the cell body. Impulses travel from neuron to neuron, from the axon of one cell to the dendrites of another, by crossing over a tiny gap between the two nerve cells called a synapse. Special chemical messengers called neurotransmitters allow the electrical impulse to cross the gap.Neurons talk to each other in the following manner (Fig. 1):
Parkinson’s Disease (PD) is a degenerative, progressive disorder that affects nerve cells in deep parts of the brain called the basal ganglia and the substantia nigra. Nerve cells in the substantia nigra produce the neurotransmitter dopamine and are responsible for relaying messages that plan and control body movement. For reasons not yet understood, the dopamine-producing nerve cells of the substantia nigra begin to die off in some individuals. When 80 percent of dopamine is lost, PD symptoms such as tremor, slowness of movement, stiffness, and balance problems occur. Body movement is controlled by a complex chain of decisions involving inter-connected groups of nerve cells called ganglia. Information comes to a central area of the brain called the striatum, which works with the substantia nigra to send impulses back and forth from the spinal cord to the brain. The basal ganglia and cerebellum are responsible for ensuring that movement is carried out in a smooth, fluid manner (Fig. 2). These impulses are passed from neuron to neuron, moving quickly from the brain to the spinal cord and, finally, to the muscles. When dopamine receptors in the striatum are not adequately stimulated, parts of the basal ganglia are either under- or over-stimulated. In particular, the subthalamic nucleus (STN) becomes overactive and acts as a brake on the globus pallidus interna (GPi), causing shutdown of motion and rigidity. When the GPi is overstimulated, it has an over-inhibitory effect on the thalamus, which in turn decreases thalamus output and causes tremor (Fig. 3). The action of dopamine is opposed by another neurotransmitter called acetylcholine. In PD the nerve cells that produce dopamine are dying. The PD symptoms of tremor and stiffness occur when the nerve cells fire and there isn't enough dopamine to transmit messages. High levels of glutamate, another neurotransmitter, also appear in PD as the body tries to compensate for the lack of dopamine.Symptoms of PD vary from person to person, as does the rate of progression. A person who has Parkinson's may experience some of these more common "hallmark" symptoms:
Other symptoms that may or may not occur:
The cause of Parkinson's is largely unknown. Doctors know much more about what PD does to the body than what causes it. Scientists are currently investigating the role that genetics, environmental factors, and the natural process of aging have on cell death and PD. There are also secondary forms of PD that are caused by medications such as haloperidol (a drug used to treat confusion and hallucinations), reserpine (an ingredient in some anti-hypertension drugs), and metoclopramide (an anti-nausea drug).More than 1.5 million Americans have PD. It usually occurs in men and women in their sixties, but can occur earlier. Early-onset Parkinson’s occurs around age 40. Because other conditions and medications mimic the symptoms of PD, getting an accurate diagnosis from a physician is important. No single test can confirm a diagnosis of PD, because the symptoms vary from person to person. A thorough history and physical exam should be enough for a diagnosis to be made. Other conditions that have Parkinson’s-like symptoms include Parkinson’s plus, essential tremor, progressive supranuclear palsy, multi-system atrophy, dystonia, and normal pressure hydrocephalus. What treatments are available? Many Parkinson's patients enjoy an active lifestyle and a normal life expectancy. Maintaining a healthy lifestyle by eating a balanced diet and staying physically active contributes to overall health and well-being. Parkinson's disease can be managed with self-care, medication, and surgery. Self careExercise is as important as medication in the treatment of PD. It helps maintain flexibility and improves balance and range of motion. Patients may want to join a support group and continue enjoyable activities to improve their quality of life. Equally important is the health and well being of the family and caregivers who are also coping with PD. For additional pointers, see Coping With Parkinson’s Disease. These are some practical tips patients can use:
There are several routes to managing Parkinson's symptoms with medication; these routes may be used alone or in combination with each other, depending on the symptoms and severity of PD.
After a time on medication, patients may notice that each dose wears off before the next dose can be taken (wearing-off effect) or erratic fluctuations in dose effect (on-off effect). Anti-Parkinson’s drugs can cause dyskinesia, which are involuntary jerking or swaying movements that typically occur at peak dosage and are caused by an overload of dopamine medication. Sometimes dyskinesia can be more troublesome than the Parkinson’s symptoms. When medications fail because of severe fluctuations in the response, lack of effectiveness, or the development of side effects, surgical therapies can be utilized to treat symptoms of tremor and rigidity. Procedures such as pallidotomy, thalamotomy, deep-brain stimulation, and transplantation are performed to target specific ganglia for destruction or stimulation (see Surgical Treatment of PD). Patients with severe depression, advanced dementia, or an unstable medical condition, and patients who have symptoms similar to PD but who have been diagnosed with a different disorder, such as Parkinson's plus or multi-system atrophy, should not consider surgical treatment.
Clinical trials are research studies in which new treatments - drugs, diagnostics, procedures, vaccines, and other therapies - are tested in people to see if they are safe and effective. Research is always being conducted to improve the standard of medical care and explore new drug and surgical treatments. You can find information about current clinical investigations, including their eligibility requirements, protocol, and participating locations on the web: the National Institutes of Health (NIH) at clinicaltrials.gov, sponsors many trials; private industry and pharmaceutical companies also sponsor trials www.centerwatch.com
If you have any questions, please call the Mayfield Clinic at 800-325-7787 or contact the American Parkinson Disease Association Information & Referral Center at 800-840-2732. Support Links axon: a long process of the nerve cell (neuron) that carries nerve impulses away from the cell body to other nerve cells. acetylcholine: a neurotransmitter that allows messages to be passed from neuron to neuron across a synapse; released by cholinergic nerves. basal ganglia: a mass of nerve cell bodies (gray matter) located deep within the white matter of the cerebrum. Has connections with areas that subconsciously control movement. bradykinesia: slowness of movement, impaired dexterity, decreased blinking, drooling, expressionless face. dendrite: the “arms” of a nerve cell that connect with the axons to transmit impulses toward the cell body. dopamine: a neurotransmitter that allows messages to be passed from neuron to neuron across a synapse. dystonia: a movement disorder that causes sustained muscle contraction producing repetitive movements or abnormal postures. Spasms can often be controlled with sensory tricks to suppress the movement. essential tremor: involuntary rhythmic tremors of the hands and arms. Tremors occur both at rest and during purposeful movement. Also affects the head in a “no-no” motion; often an inherited condition. globus pallidus interna (GPi): nuclei in the brain that regulate muscle tone; part of the basal ganglia. glutamate: a neurotransmitter that allows messages to be passed from neuron to neuron across a synapse. micrographia: small handwriting seen in Parkinson's Disease. neuron: basic unit of the nervous system, composed of a cell body, dendrites, and axon; also called a nerve cell. neurotransmitter: a chemical substance that allows for the transmission of electrical impulses from one nerve cell to another across synapses. progressive supranuclear palsy: a degenerative neurologic disorder that causes motor disturbances similar to Parkinson's. Notable symptom is the loss of ability to move the eyes to look downward. striatum (corpus striatum): part of the basal ganglia involved with the subconscious regulation of movement. substantia nigra: a group of cells in the brain where dopamine is produced. subthalamic nucleus (STN): a group of cells below the thalamus that is linked to the basal ganglia. synapse: the tiny gap between two nerve cells; across which impulses pass by release of neurotransmitters. thalamus: a relay station for all sensory messages that enter the brain; part of the basal ganglia. updated: 2.2009
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Figure 1. Neurons communicate with each other across a tiny gap called a synapse. Incoming messages from the dendrites are passed to the axon where the nerve cell is stimulated to release neurotransmitters into the synapse. The neighboring nerve cell receptors pick up these chemical messengers and effectively transmit the message onto the next nerve cell.
Figure 2. A cross section of the brain. The impulse for body movement begins in the motor cortex of the brain.
Figure 3. When the basal ganglia are over- or understimulated the
Figure 4. An electrode is precisely positioned in the desired brain area with the aid of a stereotactic head frame. Once the exact nerve cells are located, the surgeon can pass a heating current to destroy those cells or insert a stimulator to regulate those cells.
Figure 5. A deep brain stimulator electrode is placed in the desired structure of the brain. The electrode is connected to a battery implanted under the skin below the collarbone. The patient is able to turn the generator off and on with a handheld control magnet. (illustration: Medtronic Inc.)
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